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Ozcan M, Cicek C, Gok M. Exploring the GSTP1 inhibition potential of photosensitizer compounds for enhanced cancer treatment in photodynamic therapy. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:6963-6972. [PMID: 39702601 DOI: 10.1007/s00210-024-03726-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 12/10/2024] [Indexed: 12/21/2024]
Abstract
Photodynamic therapy (PDT) has gained considerable attention in cancer treatment due to its non-invasive nature and the ability of photosensitizers to generate reactive oxygen species upon light activation, leading to tumor destruction. Glutathione S-transferase P1 (GSTP1) is a key enzyme in chemotherapy resistance, often overexpressed in various cancers, and its inhibition of GSTP1 presents a promising strategy to enhance cancer treatment. This study is aimed at assessing the potential of prominent photosensitizers as GSTP1 inhibitors through molecular docking analysis to strengthen the efficacy of PDT. The photosensitizers were docked into the active site of GSTP1, and their binding affinities, inhibition constants (Ki), and molecular interactions were assessed. Among the tested photosensitizers, zinc phthalocyanine, hypericin, and temoporfin emerged as the top candidates, exhibiting binding energies of - 10.8, - 10.2, and - 9.8 kcal/mol, along with Ki values of 0.012, 0.033, and 0.064 µM, respectively. These compounds outperformed the reference inhibitor ethacrynic acid, which had a binding energy of - 6.6 kcal/mol and a Ki of 14.35 µM. These findings suggest that the dual action of these photosensitizers provides a promising strategy for combating cancer and overcoming treatment resistance.
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Affiliation(s)
- Mehmet Ozcan
- Department of Medical Biochemistry, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak, Turkey.
| | - Cigdem Cicek
- Department of Medical Biochemistry, Faculty of Medicine, Yuksek Ihtisas University, Ankara, Turkey
| | - Muslum Gok
- Department of Medical Biochemistry, Faculty of Medicine, Mugla Sitki Kocman University, Mugla, Turkey
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Benić A, Kussayeva A, Antol I, Vazdar M, Brkljača Z, Chen D, Yan Y, Gao Y, Chen Z, Margetić D. Significant Tumor Inhibition of Trimethyl-15 2-[L-aspartyl]pheophorbide a in Tumor Photodynamic Therapy ≠. ChemMedChem 2025; 20:e202500087. [PMID: 40073421 PMCID: PMC12091846 DOI: 10.1002/cmdc.202500087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 03/10/2025] [Accepted: 03/10/2025] [Indexed: 03/14/2025]
Abstract
A novel pheophorbide derivative, trimethyl-152-[L-aspartyl]pheophorbide a was synthesised and investigated for anti-tumor activity. The prepared photosensitizer had good absorption in the phototherapeutic window and high ROS yields. It exhibited excellent phototoxicity higher than reference compound m-THPC when irradiated by 650 nm light in vitro, and obvious photodynamic anti-tumor effect in vivo. It causes cellular apoptosis or necrosis under laser irradiation and localizes in mitochondria, lysosome, and endoplasmic reticulum. The observed high efficacy was rationalized by efficient introduction into the blood by facile transfer through membranes, which is supported by molecular dynamics simulation studies. This work provides a new candidate photosensitizer for anti-cancer treatment.
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Affiliation(s)
- Anita Benić
- Division of Organic Chemistry and BiochemistryRuđer Bošković InstituteBijenička c. 54Zagreb10000Croatia
| | - Akmaral Kussayeva
- Division of Organic Chemistry and BiochemistryRuđer Bošković InstituteBijenička c. 54Zagreb10000Croatia
| | - Ivana Antol
- Division of Organic Chemistry and BiochemistryRuđer Bošković InstituteBijenička c. 54Zagreb10000Croatia
| | - Mario Vazdar
- Department of MathematicsInformatics and CyberneticsUniversity of Chemistry and Technology16628PragueCzech Republic
| | - Zlatko Brkljača
- Division of Organic Chemistry and BiochemistryRuđer Bošković InstituteBijenička c. 54Zagreb10000Croatia
- Present address: Selvita d.o.o.Prilaz baruna Filipovića 2910000ZagrebCroatia
| | - Dan‐Ye Chen
- Department of Pharmaceutical Science & TechnologyDonghua UniversityShanghai201620China
| | - Yi‐Jia Yan
- Department of Pharmaceutical Science & TechnologyDonghua UniversityShanghai201620China
| | - Ying‐Hua Gao
- Department of Pharmaceutical Science & TechnologyDonghua UniversityShanghai201620China
- Department of OrthopedicsShanghai Bone Tumor InstitutionShanghai General HospitalShanghai Jiao Tong University School of Medicine100 Haining StreetShanghai200080China
| | - Zhi‐Long Chen
- Department of Pharmaceutical Science & TechnologyDonghua UniversityShanghai201620China
| | - Davor Margetić
- Division of Organic Chemistry and BiochemistryRuđer Bošković InstituteBijenička c. 54Zagreb10000Croatia
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Luo W, Wang G, Chang H, Liu G, Zhu H, Li H. Transcriptomics Uncovers Key Genes for Photodynamic Killing on Trichosporon asahii Biofilms. Mycopathologia 2025; 190:42. [PMID: 40382755 PMCID: PMC12086123 DOI: 10.1007/s11046-025-00949-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Accepted: 04/18/2025] [Indexed: 05/20/2025]
Abstract
BACKGROUND The escalating threat of antifungal resistance stemming from Trichosporon asahii (T. asahii) biofilms necessitates the pursuit of innovative therapeutic strategies. Among these approaches, 5-aminolevulinic acid (ALA) photodynamic therapy (PDT), an emerging therapeutic modality, has exhibited promising potential in eradicating T. asahii biofilms. METHODS The inhibitory activity was evaluated by confocal laser scanning microscopy. To delve deeper into the efficacy of ALA-PDT in eliminating T. asahii biofilms, we conducted a comprehensive transcriptional analysis utilizing transcriptome sequencing. RESULTS ALA-PDT demonstrated a profound inhibitory effect on the viability of T. asahii biofilms. Our investigation unveiled 2720 differentially expressed genes following exposure to ALA-PDT. Subsequent meticulous scrutiny allowed for the annotation of genes with a ≥ twofold change in transcription, focusing on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Particularly noteworthy were the upregulated genes associated with oxidation-reduction processes, oxidoreductase activity, and catalytic activity. Conversely, the downregulated genes were linked to ATP binding, protein phosphorylation, and protein kinase activity. Additionally, we observed a surge in the transcription of genes that may be involved in oxidative stress (e.g., A1Q1_05494) as well as genes that may be involved in morphogenesis and biofilm formation (e.g., A1Q1_04029, A1Q1_01345, A1Q1_08069, and A1Q1_01456) following ALA-PDT treatment. CONCLUSIONS Our findings underscore the substantial impact of ALA-PDT on the transcriptional regulation of genes related to oxidative stress, morphogenesis, and biofilm formation, paving the way for novel therapeutic avenues in combating T. asahii biofilms.
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Affiliation(s)
- Wanting Luo
- Department of Dermatology, The Seventh Medical Center of PLA General Hospital, No.5 Nanmencang, Dongcheng District, Beijing, 100700, China
- Department of Dermatology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Rd, Luohu District, Shenzhen, 518020, China
| | - Guoliang Wang
- Beijing Key Laboratory of Agricultural Genetic Resources and Biotechnology, Institute of Biotechnology, Beijing Academy of Agriculture and Forestry Sciences, No.11, Shuguang Huayuan Middle Road, Haidian District, Beijing, 100097, China
| | - Hongyu Chang
- Department of Pediatrics, the People's Liberation Army Rocket Force Characteristic Medical Center, No.6 Xinjijiekou Ouwai Street, Xicheng District, Beijing, 100088, China
| | - Guiming Liu
- Beijing Key Laboratory of Agricultural Genetic Resources and Biotechnology, Institute of Biotechnology, Beijing Academy of Agriculture and Forestry Sciences, No.11, Shuguang Huayuan Middle Road, Haidian District, Beijing, 100097, China
| | - He Zhu
- Department of Dermatology, The Seventh Medical Center of PLA General Hospital, No.5 Nanmencang, Dongcheng District, Beijing, 100700, China.
| | - Haitao Li
- Department of Dermatology, The Seventh Medical Center of PLA General Hospital, No.5 Nanmencang, Dongcheng District, Beijing, 100700, China.
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Hassan GFR, El-Amawy YSI, El Maghraby GM, Abdel-Latif AM. Photodynamic Therapy With Liquid Crystal Loaded Methylene Blue in the Treatment of Verruca. PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE 2025; 41:e70023. [PMID: 40249838 DOI: 10.1111/phpp.70023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 02/25/2025] [Accepted: 04/09/2025] [Indexed: 04/20/2025]
Abstract
BACKGROUND Verrucae (warts) are caused by human papilloma viruses. Photodynamic therapy (PDT) is a widely recommended option to treat warts. OBJECTIVES To assess the role of liquid crystal loaded methylene blue (MB) combined with intense pulsed light (IPL) in the treatment of verrucae. PATIENTS AND METHODS A total of 42 clinically and dermoscopically confirmed patients complaining of at least four cutaneous warts of various types were recruited in this clinical study. The lesions for the same patient were divided into 4 groups: Group (1) received topical 10% liquid crystal loaded MB, then was subjected to two passes of IPL with a 650 nm cutoff filter; Group (2) was subjected to two passes of IPL; and Group (3) received topical 10% liquid crystal loaded MB gel. They underwent four sessions at 2-week intervals. Group (4) was left with no treatment (control). RESULTS Complete disappearance of warts was observed in 52.4%, 19%, and 4.8% in Group 1, 2, and 3, respectively, with no recurrence throughout the following 3 months. Regarding PDT-treated group, verruca plantaris showed the best result, followed by verruca plana, then verruca vulgaris. Comparing all groups, there was a statistically significant difference in which the PDT group showed the best result. CONCLUSION PDT using 10% liquid crystal loaded MB combined with IPL is an effective option in wart treatment with the best results in V. plantaris, followed by V. plana and V. vulgaris.
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Affiliation(s)
- Ghada F R Hassan
- Professor of Dermatology and Venereology, Faculty of Medicine, Tanta University, Tanta, Egypt
| | | | - Gamal M El Maghraby
- Professor of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Amany M Abdel-Latif
- Professor of Dermatology and Venereology, Faculty of Medicine, Tanta University, Tanta, Egypt
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Osaki T, Shiomi H, Nishimura T, Sakanoue K, Eguchi K, Miyazono Y, Yamaguchi R, Fujita K, Kuwata K, Kobayashi N, Goya T, Morii K, Ota U, Imazato H, Takahashi K, Ishizuka M. 5-Aminolevulinic Acid-Mediated Metronomic Photodynamic Therapy for Mouse Mammary Tumors. Yonago Acta Med 2025; 68:114-122. [PMID: 40432740 PMCID: PMC12104577 DOI: 10.33160/yam.2025.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 03/17/2025] [Indexed: 05/29/2025]
Abstract
Background Metronomic photodynamic therapy (mPDT) is a novel cancer treatment strategy that uses low-dose light delivery and photosensitizers. 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX) was previously used to treat human colorectal and esophageal cancer cells. However, no study has evaluated the efficacy of 5-ALA-mPDT using light of different wavelengths. Therefore, we evaluated cytotoxicity induced by 5-ALA-PDT and the antitumor effect of 5-ALA-mPDT. Methods In an in vitro experiment, we evaluated the cytotoxicity induced by 5-ALA-PDT using several fluence rates of light-emitting diode (LED) at wavelengths of 532 and 620 nm. In an in vivo experiment, we evaluated the antitumor effect of 5-ALA-mPDT using a newly developed implantable device emitting 532 or 620 nm. Moreover, we used in silico simulations to compare the differences in the distribution of the accumulated singlet oxygen concentrations between 532 and 620 nm. Results In the in vitro experiment, the percentages of late apoptotic/Dead and Dead cells in the 542-nm groups irradiated at light intensities of 1 mW/cm2 were significantly higher than those of cells in the 620-nm group. In contrast, in the in vivo experiment, the antitumor effect of mPDT using an implantable organic light-emitting diode (OLED) at 620 nm was significantly higher than that of mPDT using OLED at 542 nm. Conclusion Considering the results of our in silico study, the antitumor effect of 5-ALA-mPDT may be dependent on the distribution range of the accumulated singlet oxygen concentration rather than the accumulated singlet oxygen concentration.
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Affiliation(s)
- Tomohiro Osaki
- Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan
| | - Hikaru Shiomi
- Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan
| | - Takahiro Nishimura
- Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
| | - Kei Sakanoue
- Pleiades Technologies LLC, Fukuoka 814-0001, Japan
| | | | | | - Ryoichi Yamaguchi
- Kumamoto Industrial Research Institute, Kumamoto 862-0901, Japan, ||Institute for Materials Chemistry and Engineering, Kyushu University, Fukuoka 816-8580, Japan
| | - Katsuhiko Fujita
- Institute for Materials Chemistry and Engineering, Kyushu University, Fukuoka 816-8580, Japan
| | - Kenji Kuwata
- NIPPON SHOKUBAI CO., LTD., Osaka 541-0043, Japan
| | | | | | - Katsuyuki Morii
- NIPPON SHOKUBAI CO., LTD., Osaka 541-0043, Japan
- Nippon Shokubai Research Alliance Laboratories Osaka University, Osaka 565-0871, Japan
| | - Urara Ota
- SBI Pharmaceuticals Co., Ltd., Tokyo 106-6013, Japan
| | - Hideo Imazato
- SBI Pharmaceuticals Co., Ltd., Tokyo 106-6013, Japan
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Ebeling A, Prada F. Sonodynamic Therapy Using 5-Aminolevulinic Acid for Malignant Gliomas: A Review. Life (Basel) 2025; 15:718. [PMID: 40430146 PMCID: PMC12113153 DOI: 10.3390/life15050718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Revised: 04/24/2025] [Accepted: 04/25/2025] [Indexed: 05/29/2025] Open
Abstract
In recent years, sonodynamic therapy (SDT) has attracted attention as a promising new approach for the treatment of high-grade gliomas, as it is a non-invasive form of therapy that specifically kills tumor cells with limited side effects. SDT combines low-intensity ultrasound with a sonosensitizer to produce cytotoxic effects in tumor cells. 5-Aminolevulinic acid (5-ALA), an endogenous amino acid that is metabolized to protoporphyrin IX (PpIX), has shown promise as a sonosensitizer for malignant gliomas in SDT. Ultrasound can penetrate deeper body regions and activate PpIX, leading to an increase in tumor immunogenicity and induction of apoptosis. This review highlights the current state of knowledge on the mechanisms of action, the results of preclinical, clinical and ongoing studies on 5-ALA-SDT in malignant gliomas, and discusses the future benefits of SDT.
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Affiliation(s)
- Andrea Ebeling
- Photonamic GmbH & Co KG, Eggerstedter Weg 12, 25421 Pinneberg, Germany
| | - Francesco Prada
- Department of Neurosurgery, Istituto Neurologica Carlo Besta, 20133 Milan, Italy;
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA 22903, USA
- Focused Ultrasound Foundation, Charlottesville, VA 22903, USA
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7
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Gu W. A bibliometric analysis of programmed cell death in oral cancer literature: research patterns and emerging trends (2000-2024). Discov Oncol 2025; 16:585. [PMID: 40261469 PMCID: PMC12014878 DOI: 10.1007/s12672-025-02410-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Accepted: 04/16/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Programmed cell death (PCD) plays a crucial role in oral cancer pathogenesis and treatment. However, a comprehensive bibliometric analysis of the global research landscape in this field has not been conducted. This study aims to analyze the evolution and current trends of PCD research in oral cancer from 2000 to 2024. METHODS Publications were retrieved from the Web of Science Core Collection database using relevant keywords related to oral cancer and PCD. VOSviewer 1.6.20 and CiteSpace 6.1R6 software were employed to conduct bibliometric analysis, including publication trends, citation analysis, co-authorship networks, keyword co-occurrence, and research hotspots. The time span was set from January 2000 to December 2024. RESULTS A total of 963 publications were identified and analyzed. The annual publication output showed a steady increase, with a significant growth rate after 2010, dividing the study period into three distinct phases. The most productive countries were China (58.42%), South Korea (12.27%), and Japan (10.04%), with China Medical University and Kaohsiung Medical University being the leading institutions. Research hotspots evolved from traditional apoptosis studies to emerging forms of PCD such as autophagy, ferroptosis, and pyroptosis. Keyword analysis revealed three major research clusters: basic molecular mechanisms (centered around ROS and oxidative stress), clinical aspects (including prognosis and cell proliferation), and cell death pathways. Citation burst analysis identified emerging trends in targeting multiple PCD pathways simultaneously for oral cancer therapy, with special focus on treatment resistance and survival. CONCLUSION This bibliometric analysis provides a comprehensive overview of global research trends in PCD and oral cancer over the past two decades. The findings highlight the shift from basic mechanistic studies focusing on apoptosis to more diverse PCD pathways and translational research. Emerging research directions include the exploration of synergistic mechanisms among multiple PCD pathways, development of AI-based personalized treatment plans, investigation of microenvironment regulation of PCD, and application of novel drug delivery systems. These trends demonstrate the field's evolution toward more integrated, personalized approaches in oral cancer treatment. This study offers valuable insights for researchers and funding agencies to identify research gaps and potential collaboration opportunities in this rapidly developing field.
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Affiliation(s)
- Wenli Gu
- Stomatological Hospital, School of Stomatology, Southern Medical University, S366 Jiangnan Boulevard, Haizhu District, Guangzhou, Guangdong, China.
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Gutiérrez Coronado O, Sandoval Salazar C, Muñoz Carrillo JL, Gutiérrez Villalobos OA, Miranda Beltrán MDLL, Soriano Hernández AD, Beltrán Campos V, Villalobos Gutiérrez PT. Functionalized Nanomaterials in Cancer Treatment: A Review. Int J Mol Sci 2025; 26:2633. [PMID: 40141274 PMCID: PMC11942109 DOI: 10.3390/ijms26062633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/04/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Cancer is one of the main causes of death worldwide. Chemotherapy, radiotherapy and surgery are currently the treatments of choice for cancer. However, conventional therapies have their limitations, such as non-specificity, tumor recurrence and toxicity to the target cells. Recently, nanomaterials have been considered as therapeutic agents against cancer. This is mainly due to their unique optical properties, biocompatibility, large surface area and nanoscale size. These properties are crucial as they can affect biocompatibility and uptake by the cell, reducing efficacy. However, because nanoparticles can be functionalized with biomolecules, they become more biocompatible, which improves uptake, and they can be specifically targeted against cancer cells, which improves their anticancer activity. In this review, we summarize some of the recent studies in which nanomaterials have been functionalized with the aim of increasing therapeutic efficacy in cancer treatment.
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Affiliation(s)
- Oscar Gutiérrez Coronado
- Centro Universitario de los Lagos, Universidad de Guadalajara, Lagos de Moreno 47460, Mexico; (O.G.C.); (M.d.l.L.M.B.); (A.D.S.H.)
| | - Cuauhtémoc Sandoval Salazar
- División de Ciencias de la Salud e Ingenierías, Campus Celaya-Salvatierra, Universidad de Guanajuato, Celaya 38060, Mexico; (C.S.S.); (V.B.C.)
| | - José Luis Muñoz Carrillo
- Centro Universitario de los Lagos, Universidad de Guadalajara, Lagos de Moreno 47460, Mexico; (O.G.C.); (M.d.l.L.M.B.); (A.D.S.H.)
| | | | - María de la Luz Miranda Beltrán
- Centro Universitario de los Lagos, Universidad de Guadalajara, Lagos de Moreno 47460, Mexico; (O.G.C.); (M.d.l.L.M.B.); (A.D.S.H.)
| | | | - Vicente Beltrán Campos
- División de Ciencias de la Salud e Ingenierías, Campus Celaya-Salvatierra, Universidad de Guanajuato, Celaya 38060, Mexico; (C.S.S.); (V.B.C.)
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Parizzi M, Almeida AR, Salvador G, Dominguini D, Fernandes M, Becker D, Nunes MR, Masiero AV, da Rosa CG. Photosensitized Methylene Blue Nanoparticles: A Promising Approach for the Control of Oral Infections. Biomedicines 2025; 13:673. [PMID: 40149649 PMCID: PMC11940099 DOI: 10.3390/biomedicines13030673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 03/04/2025] [Accepted: 03/06/2025] [Indexed: 03/29/2025] Open
Abstract
Introduction: Oral infections pose significant public health challenges, often exacerbating other comorbidities and increasing systemic health risks. Traditional treatments often fail to eliminate persistent micro-organisms and contribute to the rise of antimicrobial resistance. Nanoparticulate systems offer a promising solution by delivering active agents directly to targeted sites, providing more effective and localized treatment options. Objective: This study aimed to synthesize and characterize methylcellulose nanoparticles containing methylene blue at different concentrations using the nanoprecipitation method. We also evaluated their biocompatibility and antimicrobial activity against key micro-organisms commonly found in oral infections. Methods: The study involved physicochemical and morphological characterizations, including encapsulation efficiency, particle size, polydispersity index, zeta potential, and transmission electron microscopy (TEM). Additionally, controlled release profiles, antimicrobial efficacy against major oral pathogens, and biocompatibility in vitro assessments were performed. Results: The results revealed encapsulation efficiency between 99.1 and 98.8%, with particle sizes ranging from 186 to 274 nm and a zeta potential of 1.7 to 2.9 mV achieved at lower concentrations of methylene blue and methylcellulose. The nanoparticles demonstrated sustained drug release of 85% for the smaller particles and 45% for the larger particles for more than 10 h. The nanoparticles exhibited superior antimicrobial activity compared to pure methylene blue. Cell viability studies indicated that the nanoparticles were biocompatible with approximately 40% cell viability at lower concentrations of the nanoparticles. Conclusions: These findings suggest that methylene blue nanoparticles could serve as a promising adjunct in dental treatments. They offer targeted antimicrobial action while potentially reducing the development of antimicrobial resistance.
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Affiliation(s)
- Magali Parizzi
- Multi-User Laboratory, Graduate Program in Environment and Health, Planalto Catarinense University, Lages 88509-900, SC, Brazil; (M.P.); (M.F.); (A.V.M.)
| | - Aline Rosa Almeida
- Laboratory of Plasmas, Films, and Surfaces, Santa Catarina State University (UDESC), Joinville 89219-710, SC, Brazil; (A.R.A.); (D.B.)
| | - Gabriel Salvador
- Federal Institute of Santa Catarina, Lages 88506-400, SC, Brazil; (G.S.); (M.R.N.)
| | - Diogo Dominguini
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma 88806-000, SC, Brazil;
| | - Mylena Fernandes
- Multi-User Laboratory, Graduate Program in Environment and Health, Planalto Catarinense University, Lages 88509-900, SC, Brazil; (M.P.); (M.F.); (A.V.M.)
| | - Daniela Becker
- Laboratory of Plasmas, Films, and Surfaces, Santa Catarina State University (UDESC), Joinville 89219-710, SC, Brazil; (A.R.A.); (D.B.)
| | - Michael Ramos Nunes
- Federal Institute of Santa Catarina, Lages 88506-400, SC, Brazil; (G.S.); (M.R.N.)
| | - Anelise Viapiana Masiero
- Multi-User Laboratory, Graduate Program in Environment and Health, Planalto Catarinense University, Lages 88509-900, SC, Brazil; (M.P.); (M.F.); (A.V.M.)
- Department of Endodontics, College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA 52242, USA
| | - Cleonice Gonçalves da Rosa
- Multi-User Laboratory, Graduate Program in Environment and Health, Planalto Catarinense University, Lages 88509-900, SC, Brazil; (M.P.); (M.F.); (A.V.M.)
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10
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Collins VG, Hutton D, Hossain-Ibrahim K, Joseph J, Banerjee S. The abscopal effects of sonodynamic therapy in cancer. Br J Cancer 2025; 132:409-420. [PMID: 39537767 PMCID: PMC11876350 DOI: 10.1038/s41416-024-02898-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 10/24/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
The abscopal effect is a phenomenon wherein localised therapy on the primary tumour leads to regression of distal metastatic growths. Interestingly, various pre-clinical studies utilising sonodynamic therapy (SDT) have reported significant abscopal effects, however, the mechanism remains largely enigmatic. SDT is an emerging non-invasive cancer treatment that uses focussed ultrasound (FUS) and a sonosensitiser to induce tumour cell death. To expand our understanding of abscopal effects of SDT, we have summarised the preclinical studies that have found SDT-induced abscopal responses across various cancer models, using diverse combination strategies with nanomaterials, microbubbles, chemotherapy, and immune checkpoint inhibitors. Additionally, we shed light on the molecular and immunological mechanisms underpinning SDT-induced primary and metastatic tumour cell death, as well as the role and efficacy of different sonosensitisers. Notably, the observed abscopal effects underscore the need for continued investigation into the SDT-induced 'vaccine-effect' as a potential strategy for enhancing systemic anti-tumour immunity and combating metastatic disease. The results of the first SDT human clinical trials are much awaited and are hoped to enable the further evaluation of the safety and efficacy of SDT, paving the way for future studies specifically designed to explore the potential of translating SDT-induced abscopal effects into clinical reality.
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Affiliation(s)
- Victoria G Collins
- Department of Neurosurgery, Ninewells Hospital, Dundee, UK
- Department of Neurosurgery, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Dana Hutton
- The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | | | - James Joseph
- Department of Biomedical Engineering, School of Science and Engineering, University of Dundee, Dundee, UK.
| | - Sourav Banerjee
- Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK.
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Niu G, Song G, Kang Y, Zhai Y, Fan Y, Ye J, Li R, Li R, Zhang Y, Wang H, Chen Y, Ji X. Quinoidal Semiconductor Nanoparticles for NIR-II Photoacoustic Imaging and Photoimmunotherapy of Cancer. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2025; 37:e2415189. [PMID: 39696886 DOI: 10.1002/adma.202415189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 11/26/2024] [Indexed: 12/20/2024]
Abstract
Photoagents with ultra-high near-infrared II (NIR-II) light energy conversion efficiency hold great promise in tumor phototherapy due to their ability to penetrate deeper tissues and minimize damage to surrounding healthy cells. However, the development of NIR-II photoagents remain challenging. In this study, an all-fused-ring quinoidal acceptor-donor-acceptor (A-D-A) molecule, SKCN, with a BTP core is synthesized, and nanoparticles named FA-SNPs are prepared. The unique quinoidal structure enhances π-electron delocalization and bond length uniformity, significantly reducing the bandgap of SKCN, resulting in strong NIR-II absorption, a high molar extinction coefficient, and a photothermal conversion efficiency of 75.14%. Enhanced molecular rigidity also facilitates efficient energy transfer to oxygen, boosting reactive oxygen species generation. By incorporating the immunomodulator R848, FA-SRNPs nanoparticles are further developed, effectively modulating the tumor immune microenvironment by reducing Tregs and M-MDSCs infiltration, promoting dendritic cell maturation, M1 macrophage polarization, and activating CD8+ T cells and NK cells. Comprehensive studies using orthotopic ovarian cancer models demonstrated strong tumor targeting, photoacoustic imaging capabilities, and significant tumor suppression and metastasis inhibition, and also showing excellent therapeutic efficacy in an orthotopic breast cancer model. This study provides strong evidence for the potential application of quinoidal A-D-A molecules in cancer photoimmunotherapy.
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Affiliation(s)
- Gaoli Niu
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
- The First Affiliated Hospital of Henan Polytechnic University, Jiaozuo, 454000, China
| | - Guangkun Song
- State Key Laboratory and Institute of Elemento-Organic Chemistry, The Centre of Nanoscale Science and Technology and Key Laboratory of Functional Polymer Materials, Renewable Energy Conversion and Storage Center (RECAST), Tianjin Key Laboratory of Functional Polymer Materials, College of Chemistry, Nankai University, Tianjin, 300071, China
| | - Yong Kang
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Yanhong Zhai
- The First Affiliated Hospital of Henan Polytechnic University, Jiaozuo, 454000, China
| | - Yueyue Fan
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Jiamin Ye
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Ruiyan Li
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Runtan Li
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Yanwei Zhang
- Xiyingmen Subdistrict Community Health Service Center, Xiqing District, Tianjin, 300072, China
| | - Hong Wang
- The First Affiliated Hospital of Henan Polytechnic University, Jiaozuo, 454000, China
| | - Yongsheng Chen
- State Key Laboratory and Institute of Elemento-Organic Chemistry, The Centre of Nanoscale Science and Technology and Key Laboratory of Functional Polymer Materials, Renewable Energy Conversion and Storage Center (RECAST), Tianjin Key Laboratory of Functional Polymer Materials, College of Chemistry, Nankai University, Tianjin, 300071, China
| | - Xiaoyuan Ji
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
- Medical College, Linyi University, Linyi, 276000, China
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12
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Malarz K, Borzęcka W, Ziola P, Domiński A, Rawicka P, Bialik-Wąs K, Kurcok P, Torres T, Mrozek-Wilczkiewicz A. pH-sensitive phthalocyanine-loaded polymeric nanoparticles as a novel treatment strategy for breast cancer. Bioorg Chem 2025; 155:108127. [PMID: 39798455 DOI: 10.1016/j.bioorg.2025.108127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 12/15/2024] [Accepted: 01/01/2025] [Indexed: 01/15/2025]
Abstract
Novel pH-sensitive polymeric photosensitizer carriers from the phthalocyanine (Pc) group were investigated as potential photodynamic therapy drugs for the treatment of breast cancer. Their high antiproliferative activity was confirmed by photocytotoxicity studies, which indicated their high efficacy and specificity toward the SK-BR-3 cell line. Importantly, the Pcs encapsulated in the polymeric nanoparticle (NP) carrier exhibited a much better penetration into the acidic environment of tumor cells than their free form. The investigated Pc4-NPs and TT1-NPs exhibited a high selectivity to healthy fibroblasts as well as non-toxicity without irradiation. This paper describes the detailed mechanism of action of the evaluated compounds by measuring reactive oxygen species (ROS), including singlet oxygen; imaging cellular localization; and analyzing key signaling pathway proteins. An additional advantage of the evaluated compounds is their ability to inhibit the Akt protein expression, including its phosphorylation, which the Western blot test confirmed. This is particularly important because breast cancers often overexpress the HER-2 receptor-related signaling proteins. Moreover, an analysis of proteins such as GLUT-1, HO-1, phospho-p42/44, and BID revealed the significant involvement of ROS in disrupting cellular homeostasis, thereby leading to the induction of oxidative stress and resulting in apoptotic cell death.
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Affiliation(s)
- Katarzyna Malarz
- Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka 2A, 44-100 Gliwice, Poland; A. Chełkowski Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland
| | - Wioleta Borzęcka
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Marii Skłodowskiej-Curie 34, 41-819 Zabrze, Poland.
| | - Patryk Ziola
- A. Chełkowski Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland
| | - Adrian Domiński
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Marii Skłodowskiej-Curie 34, 41-819 Zabrze, Poland
| | - Patrycja Rawicka
- A. Chełkowski Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland
| | - Katarzyna Bialik-Wąs
- Department of Chemistry and Technology of Polymers, Faculty of Chemical Engineering and Technology, Cracow University of Technology, Warszawska 24, 31-155 Cracow, Poland
| | - Piotr Kurcok
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Marii Skłodowskiej-Curie 34, 41-819 Zabrze, Poland
| | - Tomas Torres
- Department of Organic Chemistry, Autonoma University of Madrid, 28049 Madrid, Spain; IMDEA-Nanociencia, Campus de Cantoblanco, c/Faraday 9, 28049 Madrid, Spain; Institute for Advanced Research in Chemical Sciences (IAdChem), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
| | - Anna Mrozek-Wilczkiewicz
- Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka 2A, 44-100 Gliwice, Poland; A. Chełkowski Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
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13
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Liang C, Liu X, Yu J, Shi L, Wei W, Zhu Y, Feng M, Tang T, Li D, Yang T, Zheng J, Ma B, Wei L. Hypericin photoactivation induces triple-negative breast cancer cells pyroptosis by targeting the ROS/CALR/Caspase-3/GSDME pathway. J Adv Res 2025:S2090-1232(25)00059-1. [PMID: 39870303 DOI: 10.1016/j.jare.2025.01.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 01/02/2025] [Accepted: 01/24/2025] [Indexed: 01/29/2025] Open
Abstract
INTRODUCTION Hypericin (HP), a natural photosensitizer, has demonstrated great efficacy in photodynamic therapy (PDT) for cancer treatment. In addition to the induction of apoptosis and necrosis through reactive oxygen species (ROS) generation, the therapeutic mechanisms and targets of PDT-HP remain unknown. OBJECTIVES To investigate the direct targets and mechanisms of action of photoactivated hypericin in the inhibition of triple-negative breast cancer (TNBC). METHODS Cell pyroptosis was examined via LDH release, SYTOX Green staining, and ELISA. RNA sequencing, network pharmacology, drug affinity target stability (DARTS)-tandem mass spectrometry (MS/MS), and molecular docking were employed to identify drug targets. Furthermore, immunoblotting and flow cytometry were utilized to elucidate the mechanisms of drug action. RESULTS Our research revealed that PDT-HP can induce pyroptosis in TNBC cells. Further investigation revealed that PDT-HP induces endoplasmic reticulum stress, activating Caspase-3 and gasdermin E (GSDME) to trigger TNBC cell pyroptosis. RNA-seq, network pharmacology, and DARTS-MS/MS proteomic analyses revealed that the endoplasmic reticulum protein calreticulin (CALR) is a potential HP target and that interfering with CALR inhibited PDT-HP-induced pyroptosis. During PDT-HP treatment, the interaction between CALR and SERCA2 inactivates SERCA2, increasing the susceptibility of cells to increased intracellular Ca2+ levels under oxidative stress. This triggered endoplasmic reticulum stress and activated Caspase3, which further cleaved GSDME, releasing GSDME-N and ultimately leading to pyroptosis in TNBC cells. CONCLUSION In this study, we provide insight into the antitumor mechanism by examining the pharmacological mechanism by which PDT-HP regulates TNBC cell pyroptosis via the ROS/CALR/Caspase-3/GSDME signaling axis.
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Affiliation(s)
- Chen Liang
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002 Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Xiao Liu
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Jie Yu
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Lingyun Shi
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Wenchao Wei
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Yalu Zhu
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Maoping Feng
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Tingting Tang
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002 Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Dameng Li
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002 Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Tao Yang
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002 Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China
| | - Junnian Zheng
- Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002 Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China.
| | - Bo Ma
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002 Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China.
| | - Liang Wei
- Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002 Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 Jiangsu, China.
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Papa V, Furci F, Minciullo PL, Casciaro M, Allegra A, Gangemi S. Photodynamic Therapy in Cancer: Insights into Cellular and Molecular Pathways. Curr Issues Mol Biol 2025; 47:69. [PMID: 39996790 PMCID: PMC11854756 DOI: 10.3390/cimb47020069] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 01/13/2025] [Accepted: 01/17/2025] [Indexed: 02/26/2025] Open
Abstract
Photodynamic therapy is a non-ionizing radiation treatment that utilizes a photosensitizer in combination with light to produce singlet oxygen. This singlet oxygen induces anti-cancer effects by causing apoptotic, necrotic, or autophagic cell death in tumor cells. Currently, photodynamic therapy is employed in oncology to treat various cancers. In the presence of oxygen, this non-invasive approach leads to direct tumor cell death, damage to microvasculature, and the induction of a local inflammatory response. These effects allow photodynamic therapy to be effective in treating early-stage tumors, extending survival in cases where surgery is not feasible, and significantly improving quality of life. In this paper, we provide a state of the art on cytomolecular mechanisms and associated pathways involved in photodynamic therapy. By integrating these mechanistic insights with the most recent advancements in nanotechnology, this phototherapeutic approach has the potential to become a prevalent treatment option within conventional cancer therapies, enhancing its application in precision medicine.
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Affiliation(s)
- Vincenzo Papa
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy; (V.P.); (P.L.M.); (S.G.)
| | - Fabiana Furci
- Provincial Healthcare Unit, Section of Allergy, 89900 Vibo Valentia, Italy;
| | - Paola Lucia Minciullo
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy; (V.P.); (P.L.M.); (S.G.)
| | - Marco Casciaro
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy; (V.P.); (P.L.M.); (S.G.)
| | - Alessandro Allegra
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, Via Consolare Valeria, 98125 Messina, Italy;
| | - Sebastiano Gangemi
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy; (V.P.); (P.L.M.); (S.G.)
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Resende PVS, Gomes INF, Peixoto MC, Stringhetta GR, Arantes LMRB, Kuzmin VA, Borissevitch I, Reis RM, de Lima Vazquez V, Ferreira LP, Oliveira RJS. Evaluation of the antineoplastic properties of the photosensitizer biscyanine in 2D and 3D tumor cell models and artificial skin models. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2024; 262:113078. [PMID: 39671777 DOI: 10.1016/j.jphotobiol.2024.113078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/20/2024] [Accepted: 11/05/2024] [Indexed: 12/15/2024]
Abstract
BACKGROUND Photodynamic Therapy (PDT) is a therapeutic modality that combines the application of a photoactive compound (photosensitizer, PS) with low-power light to generate reactive oxygen species in the target tissue, resulting in cytotoxic damage and cell death, while sparing adjacent tissues. The objective of this study was to evaluate the phototoxicity of a cyanine dye with two chromophores (biscyanines, BCD) in systems with varying levels of cellular organization, and we used the Photogem® (a photosensitizer approved by the Brazilian ANVISA agency for clinical use in Photodynamic Therapy) as a positive control. MATERIALS AND METHODS The cytotoxicity of the compounds was assessed in vitro in 2D monolayers, 3D spheroid cultures, and artificial skin models. Four tumoral cell lines A375 (melanoma), HCB-541 (cutaneous squamous cell carcinoma), Vu120T and Vu147T (head and neck cancer), and two normal cell lines fibroblastic HFF-1 and keratinocyte HACAT were used in this study. Cell viability, migration, production of reactive oxygen species, expression of proteins linked to DNA damage and repair, internalization, and skin permeation of PS agents. RESULTS Light irradiation in the presence of the PS resulted in greater cytotoxic effects for BCD as compared to Photogem®, which was accompanied by an increase in the production of reactive oxygen species including H2O2, elevated levels of cleaved PARP, and a higher rate of phosphorylated H2AX protein. BCD demonstrated enhanced internalization and bioaccumulation in the spheroids and equivalent skin models. CONCLUSION BCD, as a photosensitizer, showed higher cytotoxicity, with an increased ability to generate reactive oxygen species. This led to reduced cell viability, inhibited migration, and upregulated DNA damage-related proteins. Additionally, its enhanced cellular uptake improved skin barrier permeability, making BCD a strong candidate for in vivo Photodynamic Therapy.
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Affiliation(s)
| | | | - Maria Clara Peixoto
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
| | | | | | | | - Iouri Borissevitch
- Departamento de Física da Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, São Paulo, Brazil
| | - Rui Manuel Reis
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
| | - Vinícius de Lima Vazquez
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Department of Surgery, Melanoma and Sarcoma, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
| | | | - Renato José Silva Oliveira
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Barretos School of Health Sciences Dr. Paulo Prata-FACISB, Barretos 14785-002, SP, Brazil.
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16
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Shanazarov N, Grishacheva T, Aitkaliyev A, Salmaganbetova Z, Smailova S, Imankulova B, Afanasiev M, Dushkin A. Assessment of systemic reaction to inflammation induced by photodynamic therapy in cervical intraepithelial neoplasia. Photodiagnosis Photodyn Ther 2024; 50:104416. [PMID: 39579843 DOI: 10.1016/j.pdpdt.2024.104416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 10/28/2024] [Accepted: 11/20/2024] [Indexed: 11/25/2024]
Abstract
Photodynamic therapy is a curative treatment of human papillomavirus-associated diseases that provides a selective effect leading to the destruction of pathological cells containing the virus. The retrospective study aimed to determine the role of systemic inflammatory reaction induced by photodynamic stimulation in low- and high-squamous intraepithelial lesion treatment. METHODS 143 patients with confirmed human papillomavirus-associated cervical intraepithelial neoplasia underwent photodynamic therapy with Photolon and activation in the range of 662 nm. All patients underwent colposcopy, histologic study, HPV DNA analysis, CBC, and immunogram. The chi-square criterion was used to evaluate differences before, 5 days post, and 3 months after PDT; a P value <0.05 was considered significant. RESULTS A complete regression in patients with low-squamous intraepithelial lesion (n=117) was achieved 3 months after PDT in 89.7% of cases (105/117) while it persisted in 12 patients. Complete regression in patients with high-squamous intraepithelial lesion (n=26) was achieved in 92.3% (24/26), one patient retained with the lesion, and another one had partial regression in the form of lower grade lesion. On the 5th day post-PDT, the formation of dense fibrin in photodynamic effect was noted on colposcopy, and changes in CBC, accompanied by statistically significant neutrocytosis, increased ESR and other indicators of reactive inflammation were recorded. Patients noted increased body temperature up to 37.8±0.5°C in 88% of cases. CONCLUSION One of the mechanisms of PDT`s antitumor and antiviral action is the development of acute inflammation in response to cytotoxic action on cells and vascular response in the form of pathological area devascularization. Such reactive inflammation activates all parts of the immune system. Changes on day 5 post-PDT in inflammatory parameters in CBC and IL-1, IL-6 and TNF-α markers correlate with the clinical picture of the post-photodynamic effect.
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Affiliation(s)
- Nasrulla Shanazarov
- Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
| | - Tatyana Grishacheva
- Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russian Federation
| | - Alisher Aitkaliyev
- Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan.
| | - Zhanara Salmaganbetova
- Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
| | - Sandugash Smailova
- Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Astana, Kazakhstan
| | | | - Maxim Afanasiev
- Sechenov University, Clinical Immunology and Allergology, Moscow, Russian Federation
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17
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Sirek B, Topaloğlu N. Red wavelength-induced photobiomodulation enhances indocyanine green-based anticancer photodynamic therapy. Med Oncol 2024; 42:8. [PMID: 39560842 DOI: 10.1007/s12032-024-02558-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 11/06/2024] [Indexed: 11/20/2024]
Abstract
Cancer is a global concern worldwide. Prostate cancer has high prevalence and mortality rates among men. Photodynamic therapy (PDT) is an alternative treatment that is promising and effective with fewer side-effects than conventional therapies. However, some factors may limit its efficacy. For this, PDT can be combined with other modalities such as photobiomodulation (PBM) which is commonly used for increased cell proliferation/differentiation and wound healing. In this study, PBM pre-treatment at 655 nm of wavelength with 1, 3, and 5 J/cm2 energy densities was applied to prostate cancer cells to investigate its role in indocyanine green (ICG)-mediated PDT applications. Following PBM treatment, various analyses were assessed including cell viability, cellular uptake of ICG, ATP production, nitric oxide release, reactive oxygen species generation, and the changes in mitochondrial membrane potential. Increased cell death was observed with the PBM pre-treatment at 1 and 3 J/cm2 energy densities depending on ICG incubation time. Intracellular ROS generation and nitric oxide release by PBM had a significant impact on anticancer PDT action. An enhanced anticancer PDT effect was obtained with the PBM pre-treatment which may become a valuable modality to increase the sensitivity of the cancerous cells to PDT applications.
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Affiliation(s)
- Büşra Sirek
- Department of Biomedical Sciences, Graduate School of Natural and Applied Sciences, Izmir Katip Celebi University, Izmir, Turkey
- Department of Biomedical Engineering, Faculty of Engineering and Architecture, Izmir Katip Celebi University, Izmir, Turkey
| | - Nermin Topaloğlu
- Department of Biomedical Engineering, Faculty of Engineering and Architecture, Izmir Katip Celebi University, Izmir, Turkey.
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18
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Cui J, Makita Y, Okamura T, Ikeda C, Fujiwara SI, Tominaga K. Near-Infrared Light Photodynamic Therapy with PEI-Capped Up-Conversion Nanoparticles and Chlorin e6 Induces Apoptosis of Oral Cancer Cells. J Funct Biomater 2024; 15:333. [PMID: 39590537 PMCID: PMC11595556 DOI: 10.3390/jfb15110333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 10/31/2024] [Accepted: 11/05/2024] [Indexed: 11/28/2024] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a common malignancy in the oral cavity. Photodynamic therapy (PDT) is a new alternative for the treatment of diseases using photosensitizers (PS) and light. In this study, we used a photosensitizer complex (Ce6-MnNPs-Chlorin e6 combined with up-conversion nanoparticles NaYF4:Yb/Er/Mn) to investigate the therapeutic effectiveness of this treatment against oral cancer cells. We also investigated the mechanism of action of near-infrared light PDT (NIR-PDT) combined with the Ce6-MnNPs. After determining a suitable concentration of Ce6-MnNPs using an MTT assay, human oral squamous cell carcinoma cells (HSC-3) were treated with NIR-PDT with Ce6-MnNPs. We examined the characteristics of Ce6-MnNPs by transmission electron microscopy (TEM); a zeta potential and particle size analyzer; Fourier-transform infrared spectroscopy (FTIR); cell viability by MTT assay; and apoptosis by FITC-Annexin V/PI assay. The mitochondrial membrane potential (MMP), apoptosis-related mRNA level (Bax and Bcl-2) and p53 protein were also researched. NIR-PDT with 0.5 ng/µL Ce6-MnNPs inhibited the proliferation of HSC-3 (p < 0.05). After treatment with NIR-PDT, changes in the mitochondrial membrane potential and apoptosis occurred (p < 0.01). The ratio of Bax/Bcl-2 and p53-positive cells increased (p < 0.01). These results suggest that this treatment can induce apoptosis of oral cancer cells.
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Affiliation(s)
- Jinhao Cui
- Department of Oral Pathology, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata 573-1121, Osaka, Japan; (T.O.); (C.I.); (K.T.)
| | - Yoshimasa Makita
- Department of Chemistry, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata 573-1121, Osaka, Japan; (Y.M.); (S.-i.F.)
| | - Tomoharu Okamura
- Department of Oral Pathology, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata 573-1121, Osaka, Japan; (T.O.); (C.I.); (K.T.)
| | - Chihoko Ikeda
- Department of Oral Pathology, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata 573-1121, Osaka, Japan; (T.O.); (C.I.); (K.T.)
| | - Shin-ichi Fujiwara
- Department of Chemistry, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata 573-1121, Osaka, Japan; (Y.M.); (S.-i.F.)
| | - Kazuya Tominaga
- Department of Oral Pathology, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata 573-1121, Osaka, Japan; (T.O.); (C.I.); (K.T.)
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Lee DJ, Cao Y, Juvekar V, Sauraj, Noh CK, Shin SJ, Liu Z, Kim HM. Development of a small molecule-based two-photon photosensitizer for targeting cancer cells. J Mater Chem B 2024. [PMID: 39469993 DOI: 10.1039/d4tb01706d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/30/2024]
Abstract
Photodynamic therapy (PDT) employing two-photon (TP) excitation is increasingly recognized to induce cell damage selectively in targeted areas, underscoring the importance of developing TP photosensitizers (TP-PSs). In this study, we developed BSe-B, a novel PS that combines a selenium containing dye with biotin, a cancer-selective ligand, and is optimized for TP excitation. BSe-B demonstrated enhanced cancer selectivity, efficient generation of type-I based reactive oxygen species (ROS), low dark toxicity, and excellent cell-staining capability. Evaluation across diverse cell lines (HeLa, A549, OVCAR-3, WI-38, and L-929) demonstrated that BSe-B differentiated and targeted cancer cells while sparing normal cells. BSe-B displayed excellent in vivo biocompatibility. In cancer models such as three-dimensional spheroids and actual colon cancer tissues, BSe-B selectively induced ROS production and cell death under TP irradiation, demonstrating precise spatial control. These findings highlight the potential of BSe-B for imaging-guided PDT and its capability for micro treatment within tissues. Thus, BSe-B demonstrates robust TP-PDT capabilities, making it a promising dual-purpose tool for cancer diagnosis and treatment.
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Affiliation(s)
- Dong Joon Lee
- Department of Energy Systems Research and Department of Chemistry, Ajou University, Suwon 16499, Korea.
| | - Yu Cao
- College of Health Science and Engineering, Hubei University, Wuhan 430062, China.
| | - Vinayak Juvekar
- Department of Energy Systems Research and Department of Chemistry, Ajou University, Suwon 16499, Korea.
| | - Sauraj
- Department of Energy Systems Research and Department of Chemistry, Ajou University, Suwon 16499, Korea.
| | - Choong-Kyun Noh
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Korea.
| | - Sung Jae Shin
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Korea.
| | - Zhihong Liu
- College of Health Science and Engineering, Hubei University, Wuhan 430062, China.
| | - Hwan Myung Kim
- Department of Energy Systems Research and Department of Chemistry, Ajou University, Suwon 16499, Korea.
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20
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Zhou Y, Zou P, Chen X, Chen P, Shi M, Lang J, Chen M. Overcoming Barriers in Photodynamic Therapy Harnessing Nanogenerators Strategies. Int J Biol Sci 2024; 20:5673-5694. [PMID: 39494340 PMCID: PMC11528466 DOI: 10.7150/ijbs.100317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Accepted: 10/03/2024] [Indexed: 11/05/2024] Open
Abstract
Photodynamic therapy (PDT) represents a targeted approach for cancer treatment that employs light and photosensitizers (PSs) to induce the generation of reactive oxygen species (ROS). However, PDT faces obstacles including insufficient PS localization, limited light penetration, and treatment resistance. A potential solution lies in nanogenerators (NGs), which function as self-powered systems capable of generating electrical energy. Recent progress in piezoelectric and triboelectric NGs showcases promising applications in cancer research and drug delivery. Integration of NGs with PDT holds the promise of enhancing treatment efficacy by ensuring sustained PS illumination, enabling direct electrical control of cancer cells, and facilitating improved drug administration. This comprehensive review aims to augment our comprehension of PDT principles, explore associated challenges, and underscore the transformative capacity of NGs in conjunction with PDT. By harnessing NG technology alongside PDT, significant advancement in cancer treatment can be realized. Herein, we present the principal findings and conclusions of this study, offering valuable insights into the integration of NGs to overcome barriers in PDT.
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Affiliation(s)
- Yi Zhou
- Department of Abdominal Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Pingjin Zou
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Xingmin Chen
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Ping Chen
- Department of Abdominal Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Min Shi
- Department of Pathology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Jinyi Lang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Meihua Chen
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China
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21
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Attar GS, Kumar M, Bhalla V. Targeting sub-cellular organelles for boosting precision photodynamic therapy. Chem Commun (Camb) 2024; 60:11610-11624. [PMID: 39320942 DOI: 10.1039/d4cc02702g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2024]
Abstract
Among various cancer treatment methods, photodynamic therapy has received significant attention due to its non-invasiveness and high efficiency in inhibiting tumour growth. Recently, specific organelle targeting photosensitizers have received increasing interest due to their precise accumulation and ability to trigger organelle-mediated cell death signalling pathways, which greatly reduces the drug dosage, minimizes toxicity, avoids multidrug resistance, and prevents recurrence. In this review, recent advances and representative photosensitizers used in targeted photodynamic therapy on organelles, specifically including the endoplasmic reticulum, Golgi apparatus, mitochondria, nucleus, and lysosomes, have been comprehensively reviewed with a focus on organelle structure and organelle-mediated cell death signalling pathways. Furthermore, a perspective on future research and potential challenges in precision photodynamic therapy has been presented at the end.
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Affiliation(s)
- Gopal Singh Attar
- Department of chemistry UGC Sponsored-Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar-143005, Punjab, India.
| | - Manoj Kumar
- Department of chemistry UGC Sponsored-Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar-143005, Punjab, India.
| | - Vandana Bhalla
- Department of chemistry UGC Sponsored-Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar-143005, Punjab, India.
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22
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Marinho MAG, da Silva Marques M, de Oliveira Vian C, de Moraes Vaz Batista Filgueira D, Horn AP. Photodynamic therapy with curcumin and near-infrared radiation as an antitumor strategy to glioblastoma cells. Toxicol In Vitro 2024; 100:105917. [PMID: 39142446 DOI: 10.1016/j.tiv.2024.105917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/18/2024] [Accepted: 08/09/2024] [Indexed: 08/16/2024]
Abstract
Glioblastoma is a malignant neoplasm that develops in the central nervous system and is characterized by high rates of cell proliferation and invasion, presenting resistance to treatments and a poor prognosis. Photodynamic therapy (PDT) is a therapeutic modality that can be applied in oncological cases and stands out for being less invasive. Photosensitizers (PS) of natural origin gained prominence in PDT. Curcumin (CUR) is a natural compound that has been used in PDT, considered a promising PS. In this work, we evaluated the effects of PDT-mediated CUR and near-infrared radiation (NIR) in glioblastoma cells. Through trypan blue exclusion analysis, we chose the concentration of 5 μM of CUR and the dose of 2 J/cm2 of NIR that showed better responses in reducing the viable cell number in the C6 cell line and did not show cytotoxic/cytostatic effects in the HaCat cell line. Our results show that there is a positive interaction between CUR and NIR as a PDT model since there was an increase in ROS levels, a decrease in cell proliferation, increase in cytotoxicity with cell death by autophagy and necrosis, in addition to the presence of oxidative damage to proteins. These results suggest that the use of CUR and NIR is a promising strategy for the antitumor application of PDT.
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Affiliation(s)
- Marcelo Augusto Germani Marinho
- Programa de Pós-Graduação em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil; Laboratório de Cultura Celular, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil.
| | - Magno da Silva Marques
- Programa de Pós-Graduação em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil; Laboratório de Neurociências, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil
| | - Camila de Oliveira Vian
- Programa de Pós-Graduação em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil; Laboratório de Neurociências, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil
| | - Daza de Moraes Vaz Batista Filgueira
- Programa de Pós-Graduação em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil; Laboratório de Cultura Celular, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil
| | - Ana Paula Horn
- Programa de Pós-Graduação em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil; Laboratório de Neurociências, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS 96210-900, Brazil
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23
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Ain QT. Recent development of nanomaterials-based PDT to improve immunogenic cell death. Photochem Photobiol Sci 2024; 23:1983-1998. [PMID: 39320675 DOI: 10.1007/s43630-024-00638-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 09/11/2024] [Indexed: 09/26/2024]
Abstract
Photodynamic therapy (PDT) is a clinically approved therapeutic modality for treating oncological and non-oncological disorders. PDT has proclaimed multiple benefits over further traditional cancer therapies including its minimal systemic toxicity and selective ability to eliminate irradiated tumors. In PDT, a photosensitizing substance localizes in tumor tissues and becomes active when exposed to a particular wavelength of laser light. This produces reactive oxygen species (ROS), which induce neoplastic cells to die and lead to the regression of tumors. The contributions of ROS to PDT-induced tumor destruction are described by three basic processes including direct or indirect cell death, vascular destruction, and immunogenic cell death. However, the efficiency of PDT is significantly limited by the inherent nature and tumor microenvironment. Combining immunotherapy with PDT has recently been shown to improve tumor immunogenicity while decreasing immunoregulatory repression, thereby gently modifying the anticancer immune response with long-term immunological memory effects. This review highlights the fundamental ideas, essential elements, and mechanisms of PDT as well as nanomaterial-based PDT to boost tumor immunogenicity. Moreover, the synergistic use of immunotherapy in combination with PDT to enhance immune responses against tumors is emphasized.
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Affiliation(s)
- Qura Tul Ain
- Department of Physics, The Women University Multan, Khawajabad, Multan, Pakistan.
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24
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Lee JJC, Chua MH, Wang S, Qu Z, Zhu Q, Xu J. Cyclotriphosphazene: A Versatile Building Block for Diverse Functional Materials. Chem Asian J 2024; 19:e202400357. [PMID: 38837322 DOI: 10.1002/asia.202400357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 06/01/2024] [Accepted: 06/04/2024] [Indexed: 06/07/2024]
Abstract
Cyclotriphosphazene (CP) is a cyclic inorganic compound with the chemical formula N3P3. This unique molecule consists of a six-membered ring composed of alternating nitrogen and phosphorus atoms, each bonded to two chlorine atoms. CP exhibits remarkable versatility and significance in the realm of materials chemistry due to its easy functionalization via facile nucleophilic substitution reactions in mild conditions as well as intriguing properties of resultant final CP-based molecules or polymers. CP has been served as an important building block for numerous functional materials. This review provides a general and broad overview of the synthesis of CP-based small molecules through nucleophilic substitution of hexachlorocyclotriphosphazene (HCCP), and their applications, including flame retardants, liquid crystals (LC), chemosensors, electronics, biomedical materials, and lubricants, have been summarized and discussed. It would be expected that this review would offer a timely summary of various CP-based materials and hence give an insight into further exploration of CP-based molecules in the future.
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Affiliation(s)
- Johnathan Joo Cheng Lee
- Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis, #08-03, Singapore, Singapore, 138634
| | - Ming Hui Chua
- Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 1 Pesek Road Jurong Island, Singapore, Singapore, 627833
| | - Suxi Wang
- Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis, #08-03, Singapore, Singapore, 138634
| | - Zhengyao Qu
- State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan, 430070, China
| | - Qiang Zhu
- Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis, #08-03, Singapore, Singapore, 138634
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371
| | - Jianwei Xu
- Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis, #08-03, Singapore, Singapore, 138634
- Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 1 Pesek Road Jurong Island, Singapore, Singapore, 627833
- Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, Singapore, 117543
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25
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Niu G, Bi X, Kang Y, Zhao H, Li R, Ding M, Zhou B, Zhai Y, Ji X, Chen Y. An Acceptor-Donor-Acceptor Structured Nano-Aggregate for NIR-Triggered Interventional Photoimmunotherapy of Cervical Cancer. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2407199. [PMID: 39096075 DOI: 10.1002/adma.202407199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 07/25/2024] [Indexed: 08/04/2024]
Abstract
Compared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment with minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration and the potential for tumor resistance. Here, an acceptor-donor-acceptor (A-D-A)-structured nanoaggregate is developed with dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), triggered by single near-infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), the A-D-A-structured nanoaggregates exhibit broad absorption extending to the NIR region and effectively suppressed fluorescence, which enables deep penetration and efficient photothermal conversion (η = 67.94%). A suitable HOMO-LUMO distribution facilitates sufficient intersystem crossing (ISC) to convert ground-state oxygen (3O2) to singlet oxygen (1O2) and superoxide anions (·O2 -), and catalyze hydroxyl radical (·OH) generation. The enhanced ICT and ISC effects endow the A-D-A structured nanoaggregates with efficient PTT and PDT for cervical cancer, inducing efficient immunogenic cell death. In combination with clinical aluminum adjuvant gel, a novel photoimmunotherapy strategy for cervical cancer is developed and demonstrated to significantly inhibit primary and metastatic tumors in orthotopic and intraperitoneal metastasis cervical cancer animal models. The noninvasive therapy strategy offers new insights for clinical early-stage and advanced cervical cancer treatment.
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Affiliation(s)
- Gaoli Niu
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
- The First Affiliated Hospital of Henan Polytechnic University, Jiaozuo, 454000, China
| | - Xingqi Bi
- State Key Laboratory and Institute of Elemento-Organic Chemistry, The Centre of Nanoscale Science and Technology and Key Laboratory of Functional Polymer Materials, Renewable Energy Conversion and Storage Center (RECAST), Tianjin Key Laboratory of Functional Polymer Materials, College of Chemistry, Nankai University, Tianjin, 300071, China
| | - Yong Kang
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Hua Zhao
- Henan Reproductive Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
| | - Ruiyan Li
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Mengbin Ding
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Baoli Zhou
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Yanhong Zhai
- The First Affiliated Hospital of Henan Polytechnic University, Jiaozuo, 454000, China
| | - Xiaoyuan Ji
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
- Medical College, Linyi University, Linyi, 276000, China
| | - Yongsheng Chen
- State Key Laboratory and Institute of Elemento-Organic Chemistry, The Centre of Nanoscale Science and Technology and Key Laboratory of Functional Polymer Materials, Renewable Energy Conversion and Storage Center (RECAST), Tianjin Key Laboratory of Functional Polymer Materials, College of Chemistry, Nankai University, Tianjin, 300071, China
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26
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Kazemi KS, Kazemi P, Mivehchi H, Nasiri K, Eshagh Hoseini SS, Nejati ST, Pour Bahrami P, Golestani S, Nabi Afjadi M. Photodynamic Therapy: A Novel Approach for Head and Neck Cancer Treatment with Focusing on Oral Cavity. Biol Proced Online 2024; 26:25. [PMID: 39154015 PMCID: PMC11330087 DOI: 10.1186/s12575-024-00252-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 07/31/2024] [Indexed: 08/19/2024] Open
Abstract
Oral cancers, specifically oral squamous cell carcinoma (OSCC), pose a significant global health challenge, with high incidence and mortality rates. Conventional treatments such as surgery, radiotherapy, and chemotherapy have limited effectiveness and can result in adverse reactions. However, as an alternative, photodynamic therapy (PDT) has emerged as a promising option for treating oral cancers. PDT involves using photosensitizing agents in conjunction with specific light to target and destroy cancer cells selectively. The photosensitizers accumulate in the cancer cells and generate reactive oxygen species (ROS) upon exposure to the activating light, leading to cellular damage and ultimately cell death. PDT offers several advantages, including its non-invasive nature, absence of known long-term side effects when administered correctly, and cost-effectiveness. It can be employed as a primary treatment for early-stage oral cancers or in combination with other therapies for more advanced cases. Nonetheless, it is important to note that PDT is most effective for superficial or localized cancers and may not be suitable for larger or deeply infiltrating tumors. Light sensitivity and temporary side effects may occur but can be managed with appropriate care. Ongoing research endeavors aim to expand the applications of PDT and develop novel photosensitizers to further enhance its efficacy in oral cancer treatment. This review aims to evaluate the effectiveness of PDT in treating oral cancers by analyzing a combination of preclinical and clinical studies.
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Affiliation(s)
- Kimia Sadat Kazemi
- Faculty of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parisa Kazemi
- Faculty of Dentistry, Ilam University of Medical Sciences, Ilam, Iran
| | - Hassan Mivehchi
- Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
| | - Kamyar Nasiri
- Faculty of Dentistry, Islamic Azad University of Medical Sciences, Tehran, Iran
| | | | | | | | - Shayan Golestani
- Department of Oral and Maxillofacial Surgery, Dental School, Islamic Azad University, Isfahan, Iran.
| | - Mohsen Nabi Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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27
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Ebrahimi S, Khaleghi Ghadiri M, Stummer W, Gorji A. Enhancing 5-ALA-PDT efficacy against resistant tumor cells: Strategies and advances. Life Sci 2024; 351:122808. [PMID: 38852796 DOI: 10.1016/j.lfs.2024.122808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 05/20/2024] [Accepted: 06/04/2024] [Indexed: 06/11/2024]
Abstract
As a precursor of protoporphyrin IX (PpIX), an endogenous pro-apoptotic and fluorescent molecule, 5-Aminolevulinic acid (5-ALA) has gained substantial attention for its potential in fluorescence-guided surgery as well as photodynamic therapy (PDT). Moreover, 5-ALA-PDT has been suggested as a promising chemo-radio sensitization therapy for various cancers. However, insufficient 5-ALA-induced PpIX fluorescence and the induction of multiple resistance mechanisms may hinder the 5-ALA-PDT clinical outcome. Reduced efficacy and resistance to 5-ALA-PDT can result from genomic alterations, tumor heterogeneity, hypoxia, activation of pathways related to cell surveillance, production of nitric oxide, and most importantly, deregulated 5-ALA transporter proteins and heme biosynthesis enzymes. Understanding the resistance regulatory mechanisms of 5-ALA-PDT may allow the development of effective personalized cancer therapy. Here, we described the mechanisms underlying resistance to 5-ALA-PTD across various tumor types and explored potential strategies to overcome this resistance. Furthermore, we discussed future approaches that may enhance the efficacy of treatments using 5-ALA-PDT.
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Affiliation(s)
- Safieh Ebrahimi
- Epilepsy Research Center, Münster University, 48149 Münster, Germany; Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran 1996835911, Iran
| | | | - Walter Stummer
- Department of Neurosurgery, Münster University, 48149 Münster, Germany
| | - Ali Gorji
- Epilepsy Research Center, Münster University, 48149 Münster, Germany; Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran 1996835911, Iran; Neuroscience Research Center, Mashhad University of Medical Sciences, 9177948564 Mashhad, Iran.
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28
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Luo X, Jiao Q, Pei S, Zhou S, Zheng Y, Shao W, Xu K, Zhong W. A Photoactivated Self-Assembled Nanoreactor for Inducing Cascade-Amplified Oxidative Stress toward Type I Photodynamic Therapy in Hypoxic Tumors. Adv Healthc Mater 2024:e2401787. [PMID: 39101321 DOI: 10.1002/adhm.202401787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/22/2024] [Indexed: 08/06/2024]
Abstract
Type I photodynamic therapy (PDT) generates reactive oxygen species (ROS) through oxygen-independent photoreactions, making it a promising method for treating hypoxic tumors. However, the superoxide anion (O2∙-) generated usually exhibits a low oxidation capacity, restricting the antitumor efficacy of PDT in clinical practice. Herein, a photoactivated self-assembled nanoreactor (1-NBS@CeO2) is designed through integration of type I PDT and cerium oxide (CeO2) nanozymes for inducing cascade-amplified oxidative stress in hypoxic tumors. The nanoreactor is constructed though co-assembly of an amphiphilic peptide (1-NBS) and CeO2, giving well-dispersed spherical nanoparticles with enhanced superoxide dismutase (SOD)-like and peroxidase (POD)-like activities. Following light irradiation, 1-NBS@CeO2 undergoes type I photoreactions to generated O2∙-, which is further catalyzed by the nanoreactors, ultimately forming hypertoxic hydroxyl radical (∙OH) through cascade-amplified reactions. The PDT treatment using 1-NBS@CeO2 results in elevation of intracellular ROS and depletion of GSH content in A375 cells, thereby inducing mitochondrial dysfunction and triggering apoptosis and ferroptosis of tumor cells. Importantly, intravenous administration of 1-NBS@CeO2 alongside light irradiation showcases enhances antitumor efficacy and satisfactory biocompatibility in vivo. Together, the self-assembled nanoreactor facilitates cascade-amplified photoreactions for achieving efficacious type I PDT, which holds great promise in developing therapeutic modules towards hypoxic tumors.
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Affiliation(s)
- Xuan Luo
- Department of Chemistry, China Pharmaceutical University, Nanjing, 210009, China
| | - Qishu Jiao
- Department of Chemistry, China Pharmaceutical University, Nanjing, 210009, China
| | - Shicheng Pei
- Department of Chemistry, China Pharmaceutical University, Nanjing, 210009, China
| | - Shuyao Zhou
- Department of Chemistry, China Pharmaceutical University, Nanjing, 210009, China
| | - Yaxin Zheng
- Department of Chemistry, China Pharmaceutical University, Nanjing, 210009, China
| | - Weiyang Shao
- Department of Chemistry, China Pharmaceutical University, Nanjing, 210009, China
| | - Keming Xu
- Department of Chemistry, China Pharmaceutical University, Nanjing, 210009, China
- Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing, 210009, China
| | - Wenying Zhong
- Department of Chemistry, China Pharmaceutical University, Nanjing, 210009, China
- Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing, 210009, China
- Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing, 210009, China
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29
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Wang R, Hua S, Xing Y, Wang R, Wang H, Jiang T, Yu F. Organic dye-based photosensitizers for fluorescence imaging-guided cancer phototheranostics. Coord Chem Rev 2024; 513:215866. [DOI: 10.1016/j.ccr.2024.215866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/08/2024]
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30
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Javaid S, Qureshi IZ, Khurshid A, Afsar T, Husain FM, Khurshid M, Trembley JH, Razak S. Photoactive metabolite mediated photodynamic therapy of Rhabdomyosarcoma cell lines using medicinal plants and Doxorubicin co-treatments. BMC Complement Med Ther 2024; 24:270. [PMID: 39010043 PMCID: PMC11251096 DOI: 10.1186/s12906-024-04575-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 07/02/2024] [Indexed: 07/17/2024] Open
Abstract
BACKGROUND Medicinal plant-mediated combinational therapies have gained importance globally due to minimal side effects and enhanced treatment outcomes compared to single-drug modalities. We aimed to analyze the cytotoxic potential of each conventional treatment i.e., photodynamic therapy (PDT), chemotherapy (doxorubicin hydrochloride; Dox-HCl) with or without various concentrations of medicinal plant extracts (PE) on soft tissue cancer Rhabdomyosarcoma (RD) cell line. METHODS The Rhabdomyosarcoma (RD) cell line was cultured and treated with Photosensitizer (Photosense (AlPc4)), Chemo (Dox-HCl), and their combinations with different concentrations of each plant extract i.e., Thuja occidentalis, Moringa oleifera, Solanum surattense. For the source of illumination, a Diode laser (λ = 630 nm ± 1 nm, Pmax = 1.5 mW) was used. Photosensitizer uptake time (∼ 45 min) was optimized through spectrophotometric measurements (absorption spectroscopy). Drug response of each treatment arm was assessed post 24 h of administration using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5- 5-diphenyl-2 H- tetrazolium bromide (MTT) assay. RESULTS PE-mediated Chemo-Photodynamic therapy (PDT) exhibited synergistic effects (CI < 1). Moreover, Rhabdomyosarcoma culture pretreated with various plant extracts for 24 h exhibited significant inhibition of cell viability however most effective outcomes were shown by low and high doses of Moringa oleifera compared to other plant extracts. Post low doses treated culture with all plant extracts followed by PDT came up with more effectiveness when compared to all di-therapy treatments. CONCLUSION The general outcome of this work shows that the ethanolic plant extracts (higher doses) promote the death of cancerous cells in a dose-dependent way and combining Dox-HCl and photo-mediated photodynamic therapy can yield better therapeutic outcomes.
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Affiliation(s)
- Sumbal Javaid
- Animal Physiology Laboratory, Department of Animal Sciences, Quaid-i-Azam University, Islamabad, Pakistan
- Biophotonics and Photonanomedicine Research laboratory (BPRL), Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad, Pakistan
| | - Irfan Zia Qureshi
- Animal Physiology Laboratory, Department of Animal Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
| | - Ahmat Khurshid
- Animal Physiology Laboratory, Department of Animal Sciences, Quaid-i-Azam University, Islamabad, Pakistan
- Biophotonics and Photonanomedicine Research laboratory (BPRL), Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad, Pakistan
| | - Tayyaba Afsar
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, KSA, 11451, Saudi Arabia
| | - Fohad Mabood Husain
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Muhammad Khurshid
- School of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan
| | - Janeen H Trembley
- Minneapolis VA Health Care System Research Service, Minneapolis, MN, USA
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
| | - Suhail Razak
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, KSA, 11451, Saudi Arabia.
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Zhong J, Tang Y. Research progress on the role of reactive oxygen species in the initiation, development and treatment of breast cancer. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2024; 188:1-18. [PMID: 38387519 DOI: 10.1016/j.pbiomolbio.2024.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 02/06/2024] [Accepted: 02/19/2024] [Indexed: 02/24/2024]
Abstract
According to international cancer data, breast cancer (BC) is the leading type of cancer in women. Although significant progress has been made in treating BC, metastasis and drug resistance continue to be the primary causes of mortality for many patients. Reactive oxygen species (ROS) play a dual role in vivo: normal levels can maintain the body's normal physiological function; however, high levels of ROS below the toxicity threshold can lead to mtDNA damage, activation of proto-oncogenes, and inhibition of tumor suppressor genes, which are important causes of BC. Differences in the production and regulation of ROS in different BC subtypes have important implications for the development and treatment of BC. ROS can also serve as an important intracellular signal transduction factor by affecting the antioxidant system, activating MAPK and PI3K/AKT, and other signal pathways to regulate cell cycle and change the relationship between cells and the activity of metalloproteinases, which significantly impacts the metastasis of BC. Hypoxia in the BC microenvironment increases ROS production levels, thereby inducing the expression of hypoxia inducible factor-1α (HIF-1α) and forming "ROS- HIF-1α-ROS" cycle that exacerbates BC development. Many anti-BC therapies generate sufficient toxic ROS to promote cancer cell apoptosis, but because the basal level of ROS in BC cells exceeds that of normal cells, this leads to up-regulation of the antioxidant system, drug efflux, and apoptosis inhibition, rendering BC cells resistant to the drug. ROS crosstalks with tumor vessels and stromal cells in the microenvironment, increasing invasiveness and drug resistance in BC.
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Affiliation(s)
- Jing Zhong
- School of Public Health, Southwest Medical University, No.1, Section 1, Xianglin Road, Longmatan District, Luzhou City, Sichuan Province, China
| | - Yan Tang
- School of Public Health, Southwest Medical University, No.1, Section 1, Xianglin Road, Longmatan District, Luzhou City, Sichuan Province, China.
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32
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Wu X, Hu JJ, Yoon J. Cell Membrane as A Promising Therapeutic Target: From Materials Design to Biomedical Applications. Angew Chem Int Ed Engl 2024; 63:e202400249. [PMID: 38372669 DOI: 10.1002/anie.202400249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 02/15/2024] [Accepted: 02/18/2024] [Indexed: 02/20/2024]
Abstract
The cell membrane is a crucial component of cells, protecting their integrity and stability while facilitating signal transduction and information exchange. Therefore, disrupting its structure or impairing its functions can potentially cause irreversible cell damage. Presently, the tumor cell membrane is recognized as a promising therapeutic target for various treatment methods. Given the extensive research focused on cell membranes, it is both necessary and timely to discuss these developments, from materials design to specific biomedical applications. This review covers treatments based on functional materials targeting the cell membrane, ranging from well-known membrane-anchoring photodynamic therapy to recent lysosome-targeting chimaeras for protein degradation. The diverse therapeutic mechanisms are introduced in the following sections: membrane-anchoring phototherapy, self-assembly on the membrane, in situ biosynthesis on the membrane, and degradation of cell membrane proteins by chimeras. In each section, we outline the conceptual design or general structure derived from numerous studies, emphasizing representative examples to understand advancements and draw inspiration. Finally, we discuss some challenges and future directions in membrane-targeted therapy from our perspective. This review aims to engage multidisciplinary readers and encourage researchers in related fields to advance the fundamental theories and practical applications of membrane-targeting therapeutic agents.
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Affiliation(s)
- Xiaofeng Wu
- State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, 210096, Nanjing, China
| | - Jing-Jing Hu
- State Key Laboratory of Biogeology Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, 430074, Wuhan, China
- Department of Chemistry and Nanoscience, Ewha Womans University, 03706, Seoul, Republic of Korea
| | - Juyoung Yoon
- Department of Chemistry and Nanoscience, Ewha Womans University, 03706, Seoul, Republic of Korea
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33
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Viana Cabral F, Quilez Alburquerque J, Roberts HJ, Hasan T. Shedding Light on Chemoresistance: The Perspective of Photodynamic Therapy in Cancer Management. Int J Mol Sci 2024; 25:3811. [PMID: 38612619 PMCID: PMC11011502 DOI: 10.3390/ijms25073811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 03/18/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
The persistent failure of standard chemotherapy underscores the urgent need for innovative and targeted approaches in cancer treatment. Photodynamic therapy (PDT) has emerged as a promising photochemistry-based approach to address chemoresistance in cancer regimens. PDT not only induces cell death but also primes surviving cells, enhancing their susceptibility to subsequent therapies. This review explores the principles of PDT and discusses the concept of photodynamic priming (PDP), which augments the effectiveness of treatments like chemotherapy. Furthermore, the integration of nanotechnology for precise drug delivery at the right time and location and PDT optimization are examined. Ultimately, this study highlights the potential and limitations of PDT and PDP in cancer treatment paradigms, offering insights into future clinical applications.
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Affiliation(s)
- Fernanda Viana Cabral
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; (F.V.C.); (J.Q.A.); (H.J.R.)
| | - Jose Quilez Alburquerque
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; (F.V.C.); (J.Q.A.); (H.J.R.)
| | - Harrison James Roberts
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; (F.V.C.); (J.Q.A.); (H.J.R.)
| | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; (F.V.C.); (J.Q.A.); (H.J.R.)
- Division of Health Sciences and Technology, Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02139, USA
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34
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Turrini E, Ulfo L, Costantini PE, Saporetti R, Di Giosia M, Nigro M, Petrosino A, Pappagallo L, Kaltenbrunner A, Cantelli A, Pellicioni V, Catanzaro E, Fimognari C, Calvaresi M, Danielli A. Molecular engineering of a spheroid-penetrating phage nanovector for photodynamic treatment of colon cancer cells. Cell Mol Life Sci 2024; 81:144. [PMID: 38494579 PMCID: PMC10944812 DOI: 10.1007/s00018-024-05174-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 01/17/2024] [Accepted: 01/30/2024] [Indexed: 03/19/2024]
Abstract
Photodynamic therapy (PDT) represents an emerging strategy to treat various malignancies, including colorectal cancer (CC), the third most common cancer type. This work presents an engineered M13 phage retargeted towards CC cells through pentavalent display of a disulfide-constrained peptide nonamer. The M13CC nanovector was conjugated with the photosensitizer Rose Bengal (RB), and the photodynamic anticancer effects of the resulting M13CC-RB bioconjugate were investigated on CC cells. We show that upon irradiation M13CC-RB is able to impair CC cell viability, and that this effect depends on i) photosensitizer concentration and ii) targeting efficiency towards CC cell lines, proving the specificity of the vector compared to unmodified M13 phage. We also demonstrate that M13CC-RB enhances generation and intracellular accumulation of reactive oxygen species (ROS) triggering CC cell death. To further investigate the anticancer potential of M13CC-RB, we performed PDT experiments on 3D CC spheroids, proving, for the first time, the ability of engineered M13 phage conjugates to deeply penetrate multicellular spheroids. Moreover, significant photodynamic effects, including spheroid disruption and cytotoxicity, were readily triggered at picomolar concentrations of the phage vector. Taken together, our results promote engineered M13 phages as promising nanovector platform for targeted photosensitization, paving the way to novel adjuvant approaches to fight CC malignancies.
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Affiliation(s)
- Eleonora Turrini
- Dipartimento di Scienze per la Qualità della Vita (QUVI), Alma Mater Studiorum, Università Di Bologna, C.So D'Augusto, 237, 47921, Rimini, Italy
| | - Luca Ulfo
- Dipartimento di Farmacia e Biotecnologie (FaBiT), Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 3, 40126, Bologna, Italy
| | - Paolo Emidio Costantini
- Dipartimento di Farmacia e Biotecnologie (FaBiT), Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 3, 40126, Bologna, Italy
| | - Roberto Saporetti
- Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 2, 40126, Bologna, Italy
| | - Matteo Di Giosia
- Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 2, 40126, Bologna, Italy
| | - Michela Nigro
- Dipartimento di Farmacia e Biotecnologie (FaBiT), Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 3, 40126, Bologna, Italy
| | - Annapaola Petrosino
- Dipartimento di Farmacia e Biotecnologie (FaBiT), Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 3, 40126, Bologna, Italy
| | - Lucia Pappagallo
- Dipartimento di Farmacia e Biotecnologie (FaBiT), Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 3, 40126, Bologna, Italy
| | - Alena Kaltenbrunner
- Dipartimento di Farmacia e Biotecnologie (FaBiT), Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 3, 40126, Bologna, Italy
| | - Andrea Cantelli
- Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 2, 40126, Bologna, Italy
- CNR Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza" Unit of Bologna, Bologna, Italy
| | - Valentina Pellicioni
- Dipartimento di Scienze per la Qualità della Vita (QUVI), Alma Mater Studiorum, Università Di Bologna, C.So D'Augusto, 237, 47921, Rimini, Italy
| | - Elena Catanzaro
- Cell Death Investigation and Therapy (CDIT) Laboratory, Department of Human Structure and Repair, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Carmela Fimognari
- Dipartimento di Scienze per la Qualità della Vita (QUVI), Alma Mater Studiorum, Università Di Bologna, C.So D'Augusto, 237, 47921, Rimini, Italy
| | - Matteo Calvaresi
- Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 2, 40126, Bologna, Italy.
- Interdepartmental Center for Industrial Research (CIRI-SDV), Health Sciences and Technologies, University of Bologna, Bologna, Italy.
| | - Alberto Danielli
- Dipartimento di Farmacia e Biotecnologie (FaBiT), Alma Mater Studiorum, Università Di Bologna, Via Francesco Selmi 3, 40126, Bologna, Italy.
- Interdepartmental Center for Industrial Research (CIRI-SDV), Health Sciences and Technologies, University of Bologna, Bologna, Italy.
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Janbeih Z, Gallardo-Villagrán M, Therrien B, Diab-Assaf M, Liagre B, Benov L. Cellular Uptake and Phototoxicity Optimization of Arene Ruthenium Porphyrin Derivatives. INORGANICS 2024; 12:86. [DOI: 10.3390/inorganics12030086] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025] Open
Abstract
In this study, dinuclear and tetranuclear arene ruthenium porphyrins were synthesized and assessed for their potential as photosensitizers (PSs) in photodynamic therapy (PDT) using the Colo205 colon cancer cell line as a model system. Reactive oxygen species (ROS) production, cellular uptake, impact on cell viability, and mechanisms of cell death induced by the synthesized compounds were comprehensively investigated. Our results revealed that the number of arene ruthenium units, as well as zinc (Zn) metalation of the porphyrin core, significantly influenced ROS production and increased it two-folds compared to the Zn-free analogs. The uptake of tetra-substituted Zn-porphyrins by the cancer cells increased to 2.8 nmol/106 cells compared to 0.6 nmol/106 cells of the disubstituted Zn-free and Zn-chelating porphyrins. The anticancer photo-activity of the complexes, where the percentage of metabolic activity of disubstituted Zn-porphyrins decreased to 26% when Zn was inserted, was compared to disubstituted Zn-free analogs. A further decrease in metabolic activity was observed, when the number of arene ruthenium units increased in the tetra-substituted Zn-porphyrins and tetra-substituted Zn-free compounds, reaching 4% and 14% respectively. Moreover, the percentage of apoptotic cell deaths increased to 40% when Zn was inserted into disubstituted porphyrins, compared to disubstituted Zn-free analog, and 50% when the number of arene ruthenium units increased. Overall, the tetra-substituted Zn chelating porphyrins exhibited the highest PDT efficiency, followed by the di-substituted Zn-porphyrins. These findings underscore the importance of structural design in optimizing the efficacy of arene ruthenium porphyrins as PSs for PDT, offering valuable insights for the development of targeted cancer therapeutics.
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Affiliation(s)
- Zeinab Janbeih
- Biochemistry Department, Faculty of Medicine, Kuwait University, Kuwait City 12037, Kuwait
| | - Manuel Gallardo-Villagrán
- Univ. Limoges, LABCiS, UR 22722, Faculté de Pharmacie, F-87000 Limoges, France
- Institut de Chimie, Université de Neuchâtel, Avenue de Bellevaux 51, CH-2000 Neuchâtel, Switzerland
| | - Bruno Therrien
- Institut de Chimie, Université de Neuchâtel, Avenue de Bellevaux 51, CH-2000 Neuchâtel, Switzerland
| | - Mona Diab-Assaf
- Doctoral School of Sciences and Technology, Lebanese University, Hadath, Beirut 21219, Lebanon
| | - Bertrand Liagre
- Univ. Limoges, LABCiS, UR 22722, Faculté de Pharmacie, F-87000 Limoges, France
| | - Ludmil Benov
- Biochemistry Department, Faculty of Medicine, Kuwait University, Kuwait City 12037, Kuwait
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Dachani S, Kaleem M, Mujtaba MA, Mahajan N, Ali SA, Almutairy AF, Mahmood D, Anwer MK, Ali MD, Kumar S. A Comprehensive Review of Various Therapeutic Strategies for the Management of Skin Cancer. ACS OMEGA 2024; 9:10030-10048. [PMID: 38463249 PMCID: PMC10918819 DOI: 10.1021/acsomega.3c09780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 02/02/2024] [Accepted: 02/08/2024] [Indexed: 03/12/2024]
Abstract
Skin cancer (SC) poses a global threat to the healthcare system and is expected to increase significantly over the next two decades if not diagnosed at an early stage. Early diagnosis is crucial for successful treatment, as the disease becomes more challenging to cure as it progresses. However, identifying new drugs, achieving clinical success, and overcoming drug resistance remain significant challenges. To overcome these obstacles and provide effective treatment, it is crucial to understand the causes of skin cancer, how cells grow and divide, factors that affect cell growth, and how drug resistance occurs. In this review, we have explained various therapeutic approaches for SC treatment via ligands, targeted photosensitizers, natural and synthetic drugs for the treatment of SC, an epigenetic approach for management of melanoma, photodynamic therapy, and targeted therapy for BRAF-mutated melanoma. This article also provides a detailed summary of the various natural drugs that are effective in managing melanoma and reducing the occurrence of skin cancer at early stages and focuses on the current status and future prospects of various therapies available for the management of skin cancer.
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Affiliation(s)
- Sudharshan
Reddy Dachani
- Department
of Pharmacy Practice, College of Pharmacy, Shaqra University, Al-Dawadmi Campus, Al-Dawadmi 11961, Saudi Arabia
| | - Mohammed Kaleem
- Department
of Pharmacology, Babasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India
| | - Md. Ali Mujtaba
- Department
of Pharmaceutics, Faculty of Pharmacy, Northern
Border University, Arar 91911, Saudi Arabia
| | - Nilesh Mahajan
- Department
of Pharmaceutics, Dabasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India
| | - Sayyed A. Ali
- Department
of Pharmaceutics, Dabasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India
| | - Ali F Almutairy
- Department
of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia
| | - Danish Mahmood
- Department
of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia
| | - Md. Khalid Anwer
- Department
of Pharmaceutics, College of Pharmacy, Prince
Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia
| | - Mohammad Daud Ali
- Department
of Pharmacy, Mohammed Al-Mana College for
Medical Sciences, Abdulrazaq Bin Hammam Street, Al Safa 34222, Dammam, Saudi Arabia
| | - Sanjay Kumar
- Department
of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Uttar Pradesh 201306, India
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Oskroba A, Bartusik-Aebisher D, Myśliwiec A, Dynarowicz K, Cieślar G, Kawczyk-Krupka A, Aebisher D. Photodynamic Therapy and Cardiovascular Diseases. Int J Mol Sci 2024; 25:2974. [PMID: 38474220 DOI: 10.3390/ijms25052974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/24/2024] [Accepted: 03/01/2024] [Indexed: 03/14/2024] Open
Abstract
Cardiovascular diseases are the third most common cause of death in the world. The most common are heart attacks and stroke. Cardiovascular diseases are a global problem monitored by many centers, including the World Health Organization (WHO). Atherosclerosis is one aspect that significantly influences the development and management of cardiovascular diseases. Photodynamic therapy (PDT) is one of the therapeutic methods used for various types of inflammatory, cancerous and non-cancer diseases. Currently, it is not practiced very often in the field of cardiology. It is most often practiced and tested experimentally under in vitro experimental conditions. In clinical practice, the use of PDT is still rare. The aim of this review was to characterize the effectiveness of PDT in the treatment of cardiovascular diseases. Additionally, the most frequently used photosensitizers in cardiology are summarized.
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Affiliation(s)
- Aleksander Oskroba
- Science Club, Faculty of Medicine, Medical University of Lublin, 20-059 Lublin, Poland
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College of The Rzeszów University, 35-959 Rzeszów, Poland
| | - Angelika Myśliwiec
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Klaudia Dynarowicz
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the University of Rzeszów, 35-310 Rzeszów, Poland
| | - Grzegorz Cieślar
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 St., 41-902 Bytom, Poland
| | - Aleksandra Kawczyk-Krupka
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 St., 41-902 Bytom, Poland
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of The Rzeszów University, 35-959 Rzeszów, Poland
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Doronin A, Yakovlev VV, Bagnato VS. Photodynamic treatment of malignant melanoma with structured light: in silico Monte Carlo modeling. BIOMEDICAL OPTICS EXPRESS 2024; 15:1682-1693. [PMID: 38495709 PMCID: PMC10942715 DOI: 10.1364/boe.515962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 02/06/2024] [Accepted: 02/08/2024] [Indexed: 03/19/2024]
Abstract
In this report, we propose a novel strategy for the photodynamic approach to the treatment of melanoma, aiming to mitigate the excessive absorption and consequent thermal effects. The cornerstone of this approach is an innovative structured illumination technique that optimizes light delivery to the tissue. The methodology of this in silico study involves the development of an optical model of human skin with the presence of melanoma and an accurate simulation technique of photon transport within the complex turbid scattering medium. To assess the effectiveness of our proposed strategy, we introduced a cost function reflecting the irradiated volume and optical radiation absorption within the target area/volume occupied by malformation. By utilizing the cost function, we refine the offset illumination parameters for a variety of target system parameters, ensuring increased efficiency of photodynamic therapy. Our computer simulation results introduce a promising new path towards improved photodynamic melanoma treatments, potentially leading to better therapeutic outcomes and reduced side effects. Further experimental validation is needed to confirm these theoretical advancements, which could contribute towards revolutionizing current melanoma photodynamic treatment methodologies.
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Affiliation(s)
- Alexander Doronin
- School of Engineering and Computer Science, Victoria University of Wellington, Wellington, 6140, New Zealand
| | - Vladislav V. Yakovlev
- Department of Physics and Astronomy, Texas A&M University, College Station, Texas, USA
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA
| | - Vanderlei S. Bagnato
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA
- Institute of Physics, São Carlos, São Paulo University, Brazil
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Li Y, Li Y, Song Y, Liu S. Advances in research and application of photodynamic therapy in cholangiocarcinoma (Review). Oncol Rep 2024; 51:53. [PMID: 38334150 DOI: 10.3892/or.2024.8712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 01/18/2024] [Indexed: 02/10/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a disease characterized by insidious clinical manifestations and challenging to diagnose. Patients are usually diagnosed at an advanced stage and miss the opportunity for radical surgery. Therefore, effective palliative therapy is the main treatment approach for unresectable CCA. Current common palliative treatments include biliary drainage, chemotherapy, radiotherapy, targeted therapy and immunotherapy. However, these treatments only offer limited improvement in quality of life and survival. Photodynamic therapy (PDT) is a novel local treatment method that is considered a safe tumor ablation method for numerous cancers. It has shown good efficacy in various studies of CCA and is expected to become an important treatment for CCA. In the present study, the mechanisms of PDT in the treatment of CCA were systematically explored and the progress in the research of photosensitizers was discussed. The current study focused on the various PDT protocols and their therapeutic effects in CCA, with the objective of providing a new horizon for future research and clinical applications of PDT in the treatment of CCA.
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Affiliation(s)
- Yufeng Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
| | - Yuhang Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
| | - Yinghui Song
- Central Laboratory of Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan 410005, P.R. China
| | - Sulai Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
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Aebisher D, Przygórzewska A, Myśliwiec A, Dynarowicz K, Krupka-Olek M, Bożek A, Kawczyk-Krupka A, Bartusik-Aebisher D. Current Photodynamic Therapy for Glioma Treatment: An Update. Biomedicines 2024; 12:375. [PMID: 38397977 PMCID: PMC10886821 DOI: 10.3390/biomedicines12020375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 02/02/2024] [Accepted: 02/03/2024] [Indexed: 02/25/2024] Open
Abstract
Research on the development of photodynamic therapy for the treatment of brain tumors has shown promise in the treatment of this highly aggressive form of brain cancer. Analysis of both in vivo studies and clinical studies shows that photodynamic therapy can provide significant benefits, such as an improved median rate of survival. The use of photodynamic therapy is characterized by relatively few side effects, which is a significant advantage compared to conventional treatment methods such as often-used brain tumor surgery, advanced radiotherapy, and classic chemotherapy. Continued research in this area could bring significant advances, influencing future standards of treatment for this difficult and deadly disease.
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Affiliation(s)
- David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of the Rzeszów University, 35-959 Rzeszów, Poland
| | - Agnieszka Przygórzewska
- English Division Science Club, Medical College of the Rzeszów University, 35-025 Rzeszów, Poland;
| | - Angelika Myśliwiec
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the Rzeszów University, 35-310 Rzeszów, Poland; (A.M.); (K.D.)
| | - Klaudia Dynarowicz
- Center for Innovative Research in Medical and Natural Sciences, Medical College of the Rzeszów University, 35-310 Rzeszów, Poland; (A.M.); (K.D.)
| | - Magdalena Krupka-Olek
- Clinical Department of Internal Medicine, Dermatology and Allergology, Medical University of Silesia in Katowice, M. Sklodowskiej-Curie 10, 41-800 Zabrze, Poland; (M.K.-O.); (A.B.)
| | - Andrzej Bożek
- Clinical Department of Internal Medicine, Dermatology and Allergology, Medical University of Silesia in Katowice, M. Sklodowskiej-Curie 10, 41-800 Zabrze, Poland; (M.K.-O.); (A.B.)
| | - Aleksandra Kawczyk-Krupka
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College of the Rzeszów University, 35-025 Rzeszów, Poland;
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Sasaki I, Brégier F, Chemin G, Daniel J, Couvez J, Chkair R, Vaultier M, Sol V, Blanchard-Desce M. Hydrophilic Biocompatible Fluorescent Organic Nanoparticles as Nanocarriers for Biosourced Photosensitizers for Photodynamic Therapy. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:216. [PMID: 38276734 PMCID: PMC10819872 DOI: 10.3390/nano14020216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 01/11/2024] [Accepted: 01/15/2024] [Indexed: 01/27/2024]
Abstract
Most photosensitizers of interest for photodynamic therapy-especially porphyrinoids and chlorins-are hydrophobic. To circumvent this difficulty, the use of nanocarriers is an attractive strategy. In this perspective, we have developed highly water-soluble and biocompatible fluorescent organic nanoparticles (FONPs) made from citric acid and diethyltriamine which are then activated by ethlynene diamine as nanoplatforms for efficient photosensitizers (PSs). Purpurin 18 (Pp18) was selected as a biosourced chlorin photosensitizer combining the efficient single oxygen generation ability and suitable absorption in the biological spectral window. The simple reaction of activated FONPs with Pp18, which contains a reactive anhydride ring, yielded nanoparticles containing both Pp18 and Cp6 derivatives. These functionalized nanoparticles combine solubility in water, high singlet oxygen generation quantum yield in aqueous media (0.72) and absorption both in the near UV region (FONPS) and in the visible region (Soret band approximately 420 nm as well as Q bands at 500 nm, 560 nm, 660 nm and 710 nm). The functionalized nanoparticles retain the blue fluorescence of FONPs when excited in the near UV region but also show deep-red or NIR fluorescence when excited in the visible absorption bands of the PSs (typically at 520 nm, 660 nm or 710 nm). Moreover, these nanoparticles behave as efficient photosensitizers inducing colorectal cancer cell (HCT116 and HT-29 cell lines) death upon illumination at 650 nm. Half maximal inhibitory concentration (IC50) values down to, respectively, 0.04 and 0.13 nmol/mL were observed showing the potential of FONPs[Cp6] for the PDT treatment of cancer. In conclusion, we have shown that these novel biocompatible nanoparticles, which can be elaborated from biosourced components, both show deep-red emission upon excitation in the red region and are able to produce singlet oxygen with high efficiency in aqueous environments. Moreover, they show high PDT efficiency on colorectal cancer cells upon excitation in the deep red region. As such, these functional organic nanoparticles hold promise both for PDT treatment and theranostics.
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Affiliation(s)
- Isabelle Sasaki
- Institut des Sciences Moléculaires (ISM, UMR5255), University of Bordeaux, Centre National de la Recherche Scientifique, Institut Polytechnique de Bordeaux, Bat A12, 351 Cours de la Libération, 33405 Talence, France (J.C.)
| | - Frédérique Brégier
- Laboratoire des Agroressources, Biomolécules et Chimie pour l’Innovation en Santé (LABCiS, UR22722), University of Limoges, 87000 Limoges, France; (F.B.); (G.C.)
| | - Guillaume Chemin
- Laboratoire des Agroressources, Biomolécules et Chimie pour l’Innovation en Santé (LABCiS, UR22722), University of Limoges, 87000 Limoges, France; (F.B.); (G.C.)
| | - Jonathan Daniel
- Institut des Sciences Moléculaires (ISM, UMR5255), University of Bordeaux, Centre National de la Recherche Scientifique, Institut Polytechnique de Bordeaux, Bat A12, 351 Cours de la Libération, 33405 Talence, France (J.C.)
| | - Justine Couvez
- Institut des Sciences Moléculaires (ISM, UMR5255), University of Bordeaux, Centre National de la Recherche Scientifique, Institut Polytechnique de Bordeaux, Bat A12, 351 Cours de la Libération, 33405 Talence, France (J.C.)
| | - Rayan Chkair
- Laboratoire des Agroressources, Biomolécules et Chimie pour l’Innovation en Santé (LABCiS, UR22722), University of Limoges, 87000 Limoges, France; (F.B.); (G.C.)
| | - Michel Vaultier
- Institut des Sciences Moléculaires (ISM, UMR5255), University of Bordeaux, Centre National de la Recherche Scientifique, Institut Polytechnique de Bordeaux, Bat A12, 351 Cours de la Libération, 33405 Talence, France (J.C.)
| | - Vincent Sol
- Laboratoire des Agroressources, Biomolécules et Chimie pour l’Innovation en Santé (LABCiS, UR22722), University of Limoges, 87000 Limoges, France; (F.B.); (G.C.)
| | - Mireille Blanchard-Desce
- Institut des Sciences Moléculaires (ISM, UMR5255), University of Bordeaux, Centre National de la Recherche Scientifique, Institut Polytechnique de Bordeaux, Bat A12, 351 Cours de la Libération, 33405 Talence, France (J.C.)
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Xie K, Cheng M, He B, Li W, Zhong W. Photodynamic Therapy Combined with Liquid Nitrogen Cryotherapy and Curettage for the Treatment of Recalcitrant Periungual and Subungual Warts: Clinical Experience and Literature Review. Indian J Dermatol 2024; 69:57-62. [PMID: 38572045 PMCID: PMC10986876 DOI: 10.4103/ijd.ijd_524_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2024] Open
Abstract
Warts are caused by human papillomavirus (HPV) infection and can involve multiple parts of skin and mucosa, of which periungual and subungual warts are the most difficult to treat. Periungual or subungual wart is verruca vulgaris growing around or under the fingernail, destroying and deforming the nail and nail bed. Currently, liquid nitrogen cryotherapy and CO2 laser are often used for the treatment. Clinically, few doctors routinely use photodynamic therapy (PDT) to treat viral warts. We used PDT combined with liquid nitrogen cryotherapy and curettage to successfully treat a case of intractable periungual and subungual warts.
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Affiliation(s)
- Kuixia Xie
- From the Department of Dermatology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Meihong Cheng
- From the Department of Dermatology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Bo He
- Department of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, 221009, China
| | - Wei Li
- From the Department of Dermatology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Wenying Zhong
- From the Department of Dermatology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
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Merlin JPJ, Crous A, Abrahamse H. Nano-phototherapy: Favorable prospects for cancer treatment. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1930. [PMID: 37752098 DOI: 10.1002/wnan.1930] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 09/01/2023] [Accepted: 09/04/2023] [Indexed: 09/28/2023]
Abstract
Nanotechnology-based phototherapies have drawn interest in the fight against cancer because of its noninvasiveness, high flexibility, and precision in terms of cancer targeting and drug delivery based on its surface properties and size. Phototherapy has made remarkable development in recent decades. Approaches to phototherapy, which utilize nanomaterials or nanotechnology have emerged to contribute to advances around nanotechnologies in medicine, particularly for cancers. A brief overviews of the development of photodynamic therapy as well as its mechanism in cancer treatment is provided. We emphasize the design of novel nanoparticles utilized in photodynamic therapy while summarizing the representative progress during the recent years. Finally, to forecast important future research in this area, we examine the viability and promise of photodynamic therapy systems based on nanoparticles in clinical anticancer treatment applications and briefly make mention of the elimination of all reactive metabolites pertaining to nano formulations inside living organisms providing insight into clinical mechanistic processes. Future developments and therapeutic prospects for photodynamic treatments are anticipated. Our viewpoints might encourage scientists to create more potent phototherapy-based cancer therapeutic modalities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Affiliation(s)
- J P Jose Merlin
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
| | - Anine Crous
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
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Reghukumar C, Shamjith S, Murali VP, Ramya PK, Radhakrishnan KV, Maiti KK. Cyclometalated Ir(III) theranostic molecular probe enabled mitochondria targeted fluorescence-SERS-guided phototherapy in breast cancer cells. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2024; 250:112832. [PMID: 38142588 DOI: 10.1016/j.jphotobiol.2023.112832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 12/08/2023] [Accepted: 12/15/2023] [Indexed: 12/26/2023]
Abstract
The increased energy demands inherent in cancer cells necessitate a dependence on mitochondrial assistance for their proliferation and metastatic activity. Herein, an innovative photo-medical approach has been attempted, specifically targeting mitochondria, the cellular powerhouses, to attain therapeutic benefit. This strategy facilitates the rapid and precise initiation of apoptosis, the programmed cell death process. In this goal, we have synthesized cyclometalated Iridium (III) molecular probes, denoted as Ir-CN and Ir-H, with a nitrile (CN) and a hydrogen-functionalized bipyridine as ancillary ligands, respectively. Ir-CN has shown superior photosensitizing properties and lower dark cytotoxicity compared to Ir-H in the breast cancer cell line MCF-7, positioning it as the preferred probe for photodynamic therapy (PDT). The synthesized Ir-CN induces alterations in mitochondrial membrane potential, disrupting the respiratory chain function, and generating reactive oxygen species that activate signaling pathways leading to cell death. The CN-conjugated bipyridine ligand in Ir-CN contributes to the intense red fluorescence and the positive charge on the central metal atom facilitates specific mitochondrial colocalization (colocalization coefficient of 0.90). Together with this, the Iridium metal, with strong spin-orbit coupling, efficiently generates singlet oxygen with a quantum yield of 0.79. Consequently, the cytotoxic singlet oxygen produced by Ir-CN upon laser exposure disrupts mitochondrial processes, arresting the electron transport chain and energy production, ultimately leading to programmed cell death. This mitochondrial imbalance and apoptotic induction were dually confirmed through various apoptotic assays including Annexin V staining and by mapping the molecular level changes through surface-enhanced Raman spectroscopy (SERS). Therefore, cyclometalated Ir-CN emerges as a promising molecular probe for cancer theranostics, inducing laser-assisted mitochondrial damage, as tracked through bimodal fluorescence and SERS.
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Affiliation(s)
- Chandana Reghukumar
- Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Thiruvananthapuram 695019, Kerala, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Shanmughan Shamjith
- Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Thiruvananthapuram 695019, Kerala, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Vishnu Priya Murali
- Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Thiruvananthapuram 695019, Kerala, India
| | - Pilankatta K Ramya
- Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Thiruvananthapuram 695019, Kerala, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Kokkuvayil Vasu Radhakrishnan
- Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Thiruvananthapuram 695019, Kerala, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Kaustabh Kumar Maiti
- Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Thiruvananthapuram 695019, Kerala, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Durrani FA, Cacaccio J, Turowski SG, Dukh M, Bshara W, Curtin L, Sexton S, Spernyak JA, Pandey RK. Photobac derived from bacteriochlorophyll-a shows potential for treating brain tumor in animal models by photodynamic therapy with desired pharmacokinetics and limited toxicity in rats and dogs. Biomed Pharmacother 2023; 168:115731. [PMID: 37857248 PMCID: PMC10842770 DOI: 10.1016/j.biopha.2023.115731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 10/05/2023] [Accepted: 10/13/2023] [Indexed: 10/21/2023] Open
Abstract
Photobac is a near infrared photosensitizer (PS) derived from naturally occurring bacteriochlorophyll- a, with a potential for treating a variety of cancer types (U87, F98 and C6 tumor cells in vitro). The main objective of the studies presented herein was to evaluate the efficacy, toxicity and pharmacokinetic profile of Photobac in animals (mice, rats and dogs) and submit these results to the United States Food and Drug Administration (US FDA) for its approval to initiate Phase I human clinical trials of glioblastoma, a deadly cancer disease with no long term cure. The photodynamic therapy (PDT) efficacy of Photobac was evaluated in mice subcutaneously implanted with U87 tumors, and in rats bearing C6 tumors implanted in brain. In both tumor types, the Photobac-PDT was quite effective. The long-term cure in rats was monitored by magnetic resonance imaging (MRI) and histopathology analysis. A detailed pharmacology, pharmacokinetics and toxicokinetic study of Photobac was investigated in both non-GLP and GLP facilities at variable doses following the US FDA parameters. Safety Pharmacology studies suggest that there is no phototoxicity, cerebral or retinal toxicity with Photobac. No metabolites of Photobac were observed following incubation in rat, dog, mini-pig and human hepatocytes. Based on current biological data, Photobac-IND received the approval for Phase-I human clinical trials to treat Glioblastoma (brain cancer), which is currently underway at our institute. Photobac has also received an orphan drug status from the US FDA, because of its potential for treating Glioblastoma as no effective treatment is currently available for this deadly disease.
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Affiliation(s)
- Farukh A Durrani
- PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; Photolitec, LLC, 73 High Street, Buffalo, NY 14223, USA
| | - Joseph Cacaccio
- PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; Photolitec, LLC, 73 High Street, Buffalo, NY 14223, USA
| | - Steven G Turowski
- Translational Imaging Shared Resources, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Mykhaylo Dukh
- PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; Photolitec, LLC, 73 High Street, Buffalo, NY 14223, USA
| | - Wiam Bshara
- Department of Pathology, Pathology Network Shared Resources, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Leslie Curtin
- Comparative Oncology Shared Resources, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Sandra Sexton
- Comparative Oncology Shared Resources, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Joseph A Spernyak
- Translational Imaging Shared Resources, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Ravindra K Pandey
- PDT Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
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Chavda J, Rajwar A, Bhatia D, Gupta I. Synthesis of novel zinc porphyrins with bioisosteric replacement of Sorafenib: Efficient theranostic agents for anti-cancer application. J Inorg Biochem 2023; 249:112384. [PMID: 37776828 DOI: 10.1016/j.jinorgbio.2023.112384] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 09/11/2023] [Accepted: 09/20/2023] [Indexed: 10/02/2023]
Abstract
Novel zinc porphyrins (trans-A2B2 and A3B type) are reported containing pharmacophoric groups derived from Sorafenib at the meso-positions. The pharmacophoric and bioisosteric modification of Sorafenib was done with 2-methyl-4-nitro-N-phenylaniline. The in-vitro photo-cytotoxicity studies of zinc porphyrins on HeLa cells revealed excellent PDT based autophagy inhibition of cancer cells, with IC50 values between 6.2 to 15.4 μM. The trans-A2B2 type zinc porphyrin with two bioisosteric groups gave better cytotoxicity than A3B type. Molecular docking studies revealed excellent binding with mTOR protein kinase of the designed porphyrins. The confocal studies indicated significant ER localization of trans-A2B2 type zinc porphyrin in HeLa cells along with ROS generation. trans-A2B2 type zinc porphyrin induced ER stress in cancer cells, thereby causing elevation of Ca+2 ions in cytoplasm, which led to cancer cell death via autophagy pathway. The studies suggested that trans-A2B2 and A3B type zinc porphyrins can be developed as theranostic agents for anti-cancer applications.
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Affiliation(s)
- Jaydeepsinh Chavda
- Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj Campus, Gandhinagar, Gujarat 382355, India
| | - Anjali Rajwar
- Department of Biological Engineering, IIT Gandhinagar, Palaj Campus, Gandhinagar, Gujarat 382355, India
| | - Dhiraj Bhatia
- Department of Biological Engineering, IIT Gandhinagar, Palaj Campus, Gandhinagar, Gujarat 382355, India
| | - Iti Gupta
- Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj Campus, Gandhinagar, Gujarat 382355, India.
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Araújo JL, da Silva PB, Fonseca-Santos B, Báo SN, Chorilli M, de Souza PEN, Muehlmann LA, Azevedo RB. Photodynamic Therapy Directed to Melanoma Skin Cancer by Thermosensitive Hydrogel Containing Chlorophyll A. Pharmaceuticals (Basel) 2023; 16:1659. [PMID: 38139786 PMCID: PMC10747784 DOI: 10.3390/ph16121659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/16/2023] [Accepted: 11/21/2023] [Indexed: 12/24/2023] Open
Abstract
Melanoma, a severe form of skin cancer intricately linked to genetic and environmental factors, is predicted to reach 100,000 new cases worldwide by 2040, underscoring the need for effective and safe treatment options. In this study, we assessed the efficacy of a photosensitizer called Chlorophyll A (Chl-A) incorporated into hydrogels (HGs) made of chitosan (CS) and poloxamer 407 (P407) for Photodynamic Therapy (PDT) against the murine melanoma cell line B16-F10. The HG was evaluated through various tests, including rheological studies, SEM, and ATR-FTIR, along with cell viability assays. The CS- and P407-based HGs effectively released Chl-A and possessed the necessary properties for topical application. The photodynamic activity of the HG containing Chl-A was evaluated in vitro, demonstrating high therapeutic potential, with an IC50 of 25.99 µM-an appealing result when compared to studies in the literature reporting an IC50 of 173.8 µM for cisplatin, used as a positive control drug. The developed formulation of CS and P407-based HG, serving as a thermosensitive system for topical applications, successfully controlled the release of Chl-A. In vitro cell studies associated with PDT exhibited potential against the melanoma cell line.
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Affiliation(s)
- Joabe Lima Araújo
- Department of Genetics and Morphology, Institute of Biological Sciences, Darcy Ribeiro University Campus, University of Brasília, Brasília 70910-900, Brazil
| | - Patrícia Bento da Silva
- Department of Genetics and Morphology, Institute of Biological Sciences, Darcy Ribeiro University Campus, University of Brasília, Brasília 70910-900, Brazil
| | - Bruno Fonseca-Santos
- Department of Biotechnology, Health Sciences Institute, Federal University of Bahia, Salvador 40110-902, Brazil;
| | - Sônia Nair Báo
- Cellular Biology Department, Institute of Biological Sciences, Darcy Ribeiro University Campus, University of Brasília, Brasília 70910-900, Brazil;
| | - Marlus Chorilli
- School of Pharmaceutical Sciences, São Paulo State University, Araraquara 14800-903, Brazil;
| | | | | | - Ricardo Bentes Azevedo
- Department of Genetics and Morphology, Institute of Biological Sciences, Darcy Ribeiro University Campus, University of Brasília, Brasília 70910-900, Brazil
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Przygoda M, Bartusik-Aebisher D, Dynarowicz K, Cieślar G, Kawczyk-Krupka A, Aebisher D. Cellular Mechanisms of Singlet Oxygen in Photodynamic Therapy. Int J Mol Sci 2023; 24:16890. [PMID: 38069213 PMCID: PMC10706571 DOI: 10.3390/ijms242316890] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 11/21/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
In this review, we delve into the realm of photodynamic therapy (PDT), an established method for combating cancer. The foundation of PDT lies in the activation of a photosensitizing agent using specific wavelengths of light, resulting in the generation of reactive oxygen species (ROS), notably singlet oxygen (1O2). We explore PDT's intricacies, emphasizing its precise targeting of cancer cells while sparing healthy tissue. We examine the pivotal role of singlet oxygen in initiating apoptosis and other cell death pathways, highlighting its potential for minimally invasive cancer treatment. Additionally, we delve into the complex interplay of cellular components, including catalase and NOX1, in defending cancer cells against PDT-induced oxidative and nitrative stress. We unveil an intriguing auto-amplifying mechanism involving secondary singlet oxygen production and catalase inactivation, offering promising avenues for enhancing PDT's effectiveness. In conclusion, our review unravels PDT's inner workings and underscores the importance of selective illumination and photosensitizer properties for achieving precision in cancer therapy. The exploration of cellular responses and interactions reveals opportunities for refining and optimizing PDT, which holds significant potential in the ongoing fight against cancer.
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Affiliation(s)
- Maria Przygoda
- Students English Division Science Club, Medical College of The University of Rzeszów, 35-315 Rzeszów, Poland;
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College of The University of Rzeszów, 35-959 Rzeszów, Poland;
| | - Klaudia Dynarowicz
- Center for Innovative Research in Medical and Natural Sciences, Medical College of The University of Rzeszów, 35-310 Rzeszów, Poland;
| | - Grzegorz Cieślar
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland;
| | - Aleksandra Kawczyk-Krupka
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland;
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of The University of Rzeszów, 35-959 Rzeszów, Poland
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Banerjee SM, Acedo P, El Sheikh S, Harati R, Meecham A, Williams NR, Gerard G, Keshtgar MRS, MacRobert AJ, Hamoudi R. Combination of verteporfin-photodynamic therapy with 5-aza-2'-deoxycytidine enhances the anti-tumour immune response in triple negative breast cancer. Front Immunol 2023; 14:1188087. [PMID: 38022682 PMCID: PMC10664979 DOI: 10.3389/fimmu.2023.1188087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 09/27/2023] [Indexed: 12/01/2023] Open
Abstract
Introduction Triple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2'-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood. Methods The present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients. Results Functional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect in vitro and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease. Discussion To our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects.
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Affiliation(s)
- Shramana M. Banerjee
- Breast Unit, Royal Free London National Health Service (NHS) Foundation Trust, London, United Kingdom
- Division of Surgery and Interventional Science, University College London, London, United Kingdom
| | - Pilar Acedo
- Division of Surgery and Interventional Science, University College London, London, United Kingdom
- Institute for Liver and Digestive Health, Division of Medicine, University College London, London, United Kingdom
| | - Soha El Sheikh
- University College London (UCL) Cancer Institute, University College London, London, United Kingdom
| | - Rania Harati
- Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
| | - Amelia Meecham
- University College London (UCL) Cancer Institute, University College London, London, United Kingdom
| | - Norman R. Williams
- Division of Surgery and Interventional Science, University College London, London, United Kingdom
| | - Gareth Gerard
- University College London (UCL) Cancer Institute, University College London, London, United Kingdom
| | - Mohammed R. S. Keshtgar
- Breast Unit, Royal Free London National Health Service (NHS) Foundation Trust, London, United Kingdom
- Division of Surgery and Interventional Science, University College London, London, United Kingdom
| | - Alexander J. MacRobert
- Division of Surgery and Interventional Science, University College London, London, United Kingdom
| | - Rifat Hamoudi
- Division of Surgery and Interventional Science, University College London, London, United Kingdom
- Research Institute for Medical and Health Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
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Ibarra AMC, Aguiar EMG, Ferreira CBR, Siqueira JM, Corrêa L, Nunes FD, Franco ALDS, Cecatto RB, Hamblin MR, Rodrigues MFSD. Photodynamic therapy in cancer stem cells - state of the art. Lasers Med Sci 2023; 38:251. [PMID: 37919479 DOI: 10.1007/s10103-023-03911-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 10/14/2023] [Indexed: 11/04/2023]
Abstract
Despite significant efforts to control cancer progression and to improve oncology treatment outcomes, recurrence and tumor resistance are frequently observed in cancer patients. These problems are partly related to the presence of cancer stem cells (CSCs). Photodynamic therapy (PDT) has been developed as a therapeutic approach for solid tumors; however, it remains unclear how this therapy can affect CSCs. In this review, we focus on the effects of PDT on CSCs and the possible changes in the CSC population after PDT exposure. Tumor response to PDT varies according to the photosensitizer and light parameters employed, but most studies have reported the successful elimination of CSCs after PDT. However, some studies have reported that CSCs were more resistant to PDT than non-CSCs due to the increased efflux of photosensitizer molecules and the action of autophagy. Additionally, using different PDT approaches to target the CSCs resulted in increased sensitivity, reduction of sphere formation, invasiveness, stem cell phenotype, and improved response to chemotherapy. Lastly, although mainly limited to in vitro studies, PDT, combined with targeted therapies and/or chemotherapy, could successfully target CSCs in different solid tumors and promote the reduction of stemness, suggesting a promising therapeutic approach requiring evaluation in robust pre-clinical studies.
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Affiliation(s)
- Ana Melissa C Ibarra
- Postgraduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University - UNINOVE, São Paulo, Brazil
| | | | - Cássia B R Ferreira
- Postgraduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University - UNINOVE, São Paulo, Brazil
| | | | - Luciana Corrêa
- School of Dentistry, University of São Paulo - FOUSP, São Paulo, Brazil
| | - Fabio D Nunes
- School of Dentistry, University of São Paulo - FOUSP, São Paulo, Brazil
| | | | - Rebeca B Cecatto
- Postgraduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University - UNINOVE, São Paulo, Brazil
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Johannesburg, South Africa
| | - Maria Fernanda S D Rodrigues
- Postgraduate Program in Biophotonics Applied to Health Sciences, Nove de Julho University - UNINOVE, São Paulo, Brazil.
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