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Yadav PK, Chauhan D, Yadav P, Tiwari AK, Sultana N, Gupta D, Mishra K, Gayen JR, Wahajuddin M, Chourasia MK. Nanotechnology Assisted Drug Delivery Strategies for Chemotherapy: Recent Advances and Future Prospects. ACS APPLIED BIO MATERIALS 2025; 8:3601-3622. [PMID: 40318022 DOI: 10.1021/acsabm.5c00046] [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] [Indexed: 05/07/2025]
Abstract
In pursuit of the treatment of cancer, nanotechnology engineering has emerged as the simplest and most effective means, with the potential to deliver antitumor chemotherapeutics at the targeted site. Employing nanotechnology for drug delivery provides diverse nanosize particles ranging from one to a thousand nanometers. Reduced size improves drug bioavailability by increasing drug diffusion and decreasing the efflux rate. These nanocarriers offer an enormous scope for modification following the chemical and biological properties of both the drug and its disease. Moreover, these nanoformulations assist in targeting pharmaceutically active drug molecules to the desired site and have gained importance in recent years. Their modern use has revolutionized the antitumor action of many therapeutic agents. Higher drug loading efficiency, thermal stability, easy fabrication, low production cost, and large-scale industrial production draw attention to the application of nanotechnology as a better platform for the delivery of drug molecules. Furthermore, the interaction of nanocarrier technology-assisted agents lowers a drug's toxicity and therapeutic dosage, reduces drug tolerance, and enhances active drug concentration in neoplasm tissue, thus decreasing the concentration in healthy tissue. Nanotechnology-based medications are being widely explored and have depicted effective cancer management in vivo and in vitro systems, leading to many clinical trials with promising results. This review summarizes the innovative impact and application of different nanocarriers developed in recent years in cancer therapy. Subsequently, it also describes the essential findings and methodologies and their effects on cancer treatment. Compared with conventional therapy, nanomedicines can significantly improve the therapeutic effectiveness of antitumor drugs. Thus, the adverse effects associated with healthy tissues are decreased, and adverse effects are scaled back through enhanced permeability and retention effects. Lastly, future insights assisting nanotechnology in active therapeutics delivery and their scope in cancer chemotherapeutics have also been discussed.
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Affiliation(s)
- Pavan K Yadav
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Divya Chauhan
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Pooja Yadav
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Amrendra K Tiwari
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Nazneen Sultana
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
| | - Deepak Gupta
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
| | - Keerti Mishra
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
| | - Jiaur R Gayen
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
| | - Muhammad Wahajuddin
- Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP, United Kingdom
| | - Manish K Chourasia
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
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Makuch S, Kupczyk P, Woźniak M, Makarec A, Lipińska M, Klyta M, Sulecka-Zadka J, Szeja W, Gani M, Rapozzi V, Ziółkowski P, Smoleński P. In Vitro and In Vivo Antipsoriatic Efficacy of Protected and Unprotected Sugar-Zinc Phthalocyanine Conjugates. Pharmaceutics 2024; 16:838. [PMID: 38931958 PMCID: PMC11207564 DOI: 10.3390/pharmaceutics16060838] [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: 04/30/2024] [Revised: 06/12/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024] Open
Abstract
Psoriasis, a chronic immune-mediated skin disorder affecting over 125 million people globally, is characterized by abnormal keratinocyte proliferation and immune cell infiltration. Photodynamic therapy (PDT) remains underutilized in the treatment of psoriasis despite its potential as a promising and effective therapeutic approach. This study aimed to explore the efficacy of zinc phthalocyanine (ZnPc) and its sugar conjugates as potential antipsoriatic agents. We successfully synthesized protected and unprotected sugar-conjugated zinc phthalocyanines and evaluated their potential against cytokine-stimulated HaCaT keratinocytes, as well as an established IMQ psoriasis-like in vivo model. Tetrasubstituted protected glucose-ZnPc (Glu-4-ZnPc-P) demonstrated superior phototoxicity (IC50 = 2.55 µM) compared to unprotected glucose conjugate (IC50 = 22.7 µM), protected galactose-ZnPc (IC50 = 7.13 µM), and free ZnPc in cytokine-stimulated HaCaT cells (IC50 = 5.84 µM). Cellular uptake analysis revealed that IL-17A, a cytokine that plays a central role in the pathogenesis of psoriasis, enhanced unprotected Glu-4-ZnPc uptake by 56.3%, while GLUT1 inhibitor BAY-876 reduced its accumulation by 23.8%. Intracellular ROS generation following Glu-4-ZnPc-P-PDT was significantly increased after stimulation with IL-17A, correlating with in vitro photocytotoxicity. In vivo PDT using Glu-4-ZnPc-P exhibited significant improvement in Psoriasis Area and Severity Index (PASI), inhibiting splenomegaly and restoring normal skin morphology. This study highlights sugar-conjugated zinc phthalocyanines as potential candidates for targeted PDT in psoriasis, providing a basis for further clinical investigations.
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Affiliation(s)
- Sebastian Makuch
- Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (P.K.); (M.W.); (A.M.); (P.Z.)
| | - Piotr Kupczyk
- Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (P.K.); (M.W.); (A.M.); (P.Z.)
| | - Marta Woźniak
- Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (P.K.); (M.W.); (A.M.); (P.Z.)
| | - Alicja Makarec
- Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (P.K.); (M.W.); (A.M.); (P.Z.)
| | - Maja Lipińska
- Experimental Animal Facility, Wroclaw Medical University, 50-368 Wroclaw, Poland; (M.L.); (M.K.)
| | - Magdalena Klyta
- Experimental Animal Facility, Wroclaw Medical University, 50-368 Wroclaw, Poland; (M.L.); (M.K.)
| | - Joanna Sulecka-Zadka
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland;
| | - Wiesław Szeja
- Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland;
| | - Mariachiara Gani
- Department of Medicine, Laboratory of Biochemistry, P.le Kolbe 4, 33100 Udine, Italy; (M.G.); (V.R.)
| | - Valentina Rapozzi
- Department of Medicine, Laboratory of Biochemistry, P.le Kolbe 4, 33100 Udine, Italy; (M.G.); (V.R.)
| | - Piotr Ziółkowski
- Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland; (P.K.); (M.W.); (A.M.); (P.Z.)
| | - Piotr Smoleński
- Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wroclaw, Poland
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Surur AK, de Oliveira AB, De Annunzio SR, Ferrisse TM, Fontana CR. Bacterial resistance to antimicrobial photodynamic therapy: A critical update. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2024; 255:112905. [PMID: 38703452 DOI: 10.1016/j.jphotobiol.2024.112905] [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: 11/01/2023] [Revised: 03/06/2024] [Accepted: 04/04/2024] [Indexed: 05/06/2024]
Abstract
Bacterial antibiotic resistance is one of the most significant challenges for public health. The increase in bacterial resistance, mainly due to microorganisms harmful to health, and the need to search for alternative treatments to contain infections that cannot be treated by conventional antibiotic therapy has been aroused. An alternative widely studied in recent decades is antimicrobial photodynamic therapy (aPDT), a treatment that can eliminate microorganisms through oxidative stress. Although this therapy has shown satisfactory results in infection control, it is still controversial in the scientific community whether bacteria manage to develop resistance after successive applications of aPDT. Thus, this work provides an overview of the articles that performed successive aPDT applications in models using bacteria published since 2010, focusing on sublethal dose cycles, highlighting the main PSs tested, and addressing the possible mechanisms for developing tolerance or resistance to aPDT, such as efflux pumps, biofilm formation, OxyR and SoxRS systems, catalase and superoxide dismutase enzymes and quorum sensing.
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Affiliation(s)
- Amanda Koberstain Surur
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Clinical Analysis, Araraquara, São Paulo, Brazil.
| | - Analú Barros de Oliveira
- São Paulo State University (UNESP), School of Dentistry, Department of Dental Materials and Prosthodontics, Araraquara, São Paulo, Brazil.
| | - Sarah Raquel De Annunzio
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Clinical Analysis, Araraquara, São Paulo, Brazil.
| | - Túlio Morandin Ferrisse
- São Paulo State University (UNESP), School of Dentistry, Department of Dental Materials and Prosthodontics, Araraquara, São Paulo, Brazil.
| | - Carla Raquel Fontana
- São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Clinical Analysis, Araraquara, São Paulo, Brazil.
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Didamson OC, Chandran R, Abrahamse H. Aluminium phthalocyanine-mediated photodynamic therapy induces ATM-related DNA damage response and apoptosis in human oesophageal cancer cells. Front Oncol 2024; 14:1338802. [PMID: 38347844 PMCID: PMC10859414 DOI: 10.3389/fonc.2024.1338802] [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] [Received: 11/15/2023] [Accepted: 01/10/2024] [Indexed: 02/15/2024] Open
Abstract
Introduction Photodynamic therapy (PDT) is a light-based technique used in the treatment of malignant and non-malignant tissue. Aluminium-phthalocyanine chloride tetra sulfonate (AlPcS4Cl)-mediated PDT has been well investigated on several cancer types, including oesophageal cancer. However, the effects of (AlPcS4Cl)-mediated PDT on DNA damage response and the mechanism of cell death in oesophageal cancer needs further investigation. Methods Here, we examined the in vitro effects of AlPcS4Cl-mediated PDT on cell cycle, DNA damage response, oxidative stress, and intrinsic apoptotic cell death pathway in HKESC-1 oesophageal cancer cells. The HKESC-1 cells were exposed to PDT using a semiconductor laser diode (673.2 nm, 5 J/cm2 fluency). Cell viability and cytotoxicity were determined by the ATP cell viability assay and the lactate dehydrogenase (LDH) release assay, respectively. Cell cycle and DNA damage response (DDR) analyses were conducted using the Muse™ cell cycle kit and the Muse® multi-color DNA damage kit, respectively. The mode of cell death was identified using the Annexin V-FITC/PI detection assay and Muse® Autophagy LC3 antibody-based kit. The intrinsic apoptotic pathway was investigated by measuring the cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm) function, cytochrome c levels and the activity of caspase 3/7 enzymes. Results The results show that AlPcS4Cl-based PDT reduced cell viability, induced cytotoxicity, cell cycle arrest at the G0/G1 phase, and DNA double-strand break (DSB) through the upregulation of the ataxia telangiectasia mutated (ATM), a DNA damage sensor. In addition, the findings showed that AlPcS4Cl-based PDT induced cell death via apoptosis, which is observed through increased ROS production, reduced ΔΨm, increased cytochrome c release, and activation of caspase 3/7 enzyme. Finally, no autophagy was observed in the AlPcS4Cl-mediated PDT-treated cells. Conclusion Our findings showed that apoptotic cell death is the main cell death mechanism triggered by AlPcS4Cl-mediated PDT in oesophageal cancer cells.
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Affiliation(s)
| | | | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
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Rajabi N, Mohammadnejad F, Doustvandi MA, Shadbad MA, Amini M, Tajalli H, Mokhtarzadeh A, Baghbani E, Silvestris N, Baradaran B. Photodynamic therapy with zinc phthalocyanine enhances the anti-cancer effect of tamoxifen in breast cancer cell line: Promising combination treatment against triple-negative breast cancer? Photodiagnosis Photodyn Ther 2022; 41:103212. [PMID: 36436735 DOI: 10.1016/j.pdpdt.2022.103212] [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: 04/06/2022] [Revised: 11/12/2022] [Accepted: 11/23/2022] [Indexed: 11/27/2022]
Abstract
Photodynamic therapy (PDT) is a light-based anti-neoplastic therapeutic approach. Growing evidence indicates that combining conventional anti-cancer therapies with PDT can be a promising approach to treat malignancies. Herein, we aimed to investigate anti-cancer effects of the combination treatment of zinc phthalocyanine (ZnPc)-PDT with tamoxifen (TA) on MDA-MB-231 cells (as a triple-negative breast cancer (TNBC) cell line). For this purpose, we investigated the cytotoxicity of TA and ZnPc-PDT on MDA-MB-231 cells performing the MTT assay. The effect of TA and ZnPc-PDT on the apoptosis of MDA-MB-231 cells was studied using Annexin V/PI and DAPI staining. The wound-healing assay, and colony formation assay were performed to study the effect of TA and ZnPc-PDT on the migration, and clonogenicity of MDA-MB-231 cells, respectively. The qRT-PCR was done to study the gene expression of caspase-8, caspase-9, caspase-3, ZEB1, ROCK1, SNAIL1, CD133, CD44, SOX2, and ABCG2 (ATP-binding cassette sub-family G member 2). Based on our results, monotherapies with TA and ZnPc-PDT can remarkably increase cell cytotoxicity effects, stimulate apoptosis via downregulating Bcl-2 and upregulating caspase-3 and caspase-9, inhibit migration via downregulating SNAIL1 and ZEB1, and suppress clonogenicity via downregulating SOX2 and CD44 in MDA-MB-231 cells. Besides, these monotherapies can downregulate the expression of ABCG2 in MDA-MB-231 cells. Nevertheless, the combination treatment can potentiate the above-mentioned anti-cancer effects compared to monotherapy with TA. Of interest, the combined treatment of TA with ZnPc-PDT can synergically increase cell cytotoxicity effects on MDA-MB-231 cells. In fact, synergistic effects were estimated by calculation of Combination Index (CI); that synergistic outcomes were observed in all groups. Also, this combination treatment can significantly upregulate the caspase-8 gene expression and downregulate ROCK1 and CD133 gene expression in MDA-MB-231 cells. Overall, our results show that ZnPc-PDT can more sensitize the MDA-MB-231 cells to TA treatment. Based on our knowledge and experiment, the synergistic effects of ZnPc-PDT and TA deserve further evaluation in cancer research.
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Affiliation(s)
- Neda Rajabi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mohammad Amin Doustvandi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mohammad Amini
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Habib Tajalli
- Biophotonic Research Center, Islamic Azad University, Tabriz Branch, Tabriz, Iran; Research Institute for Applied Physics and Astronomy, University of Tabriz, Tabriz, Iran
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Baghbani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nicola Silvestris
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy.
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Ayaz F, Yetkin D, Yüzer A, Demircioğlu K, Ince M. Non-canonical anti-cancer, anti-metastatic, anti-angiogenic and immunomodulatory PDT potentials of water soluble phthalocyanine derivatives with imidazole groups and their intracellular mechanism of action. Photodiagnosis Photodyn Ther 2022; 39:103035. [PMID: 35905830 DOI: 10.1016/j.pdpdt.2022.103035] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/22/2022] [Accepted: 07/25/2022] [Indexed: 12/13/2022]
Abstract
Cancer is currently a leading health issue globally. Chemotherapy is a prominent treatment method but due to undesired side effects t, there has been a need for novel less toxic approaches. Photodynamic therapy may be listed among the alternatives for efficient and potentially less detrimental applications of cancer therapy. Canonical photodynamic therapy (PDT) approach requires a light source with a specific wavelength of light, a non-toxic photosensitizer and molecular oxygen. PDT creates the desired effect by the photochemical reaction created through interaction of these components to create reactive oxygen species that will act on the cancer cells to enable anti-cancer activities. In our study we focus on non-canonical PDT application. In this approach we are not only aiming to eliminate cancer cells in the environment but also test the anti-metastatic, anti-angiogenic and possible immunomodulatory activities of the novel photosensitizers. Moreover, in our approach, we studied the intracellular pathways that are crucial for carcinogenesis, cell cycle, apoptosis, angiogenesis, metastasis and immune function to decipher the mechanism of the action for each compound. Reactive oxygen species based explanation was not valid in our study, hence it brings out a non canonical approach to PDT applications. Our results suggests that Phthalocyanine derivatives with imidazole groups can be effectively used against lung, colon, breast and prostate cancer while differentially effecting metastasis, angiogenesis, cell cycle, apoptosis and immune system cells' activities. Based on the results, PDT application of these phthalocyanine derivatives can be an effective treatment option to replace chemotherapy to minimize the potential side effects.
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Affiliation(s)
- Furkan Ayaz
- Department of Biotechnology, Faculty of Arts and Science, Mersin University, Mersin 33110, Turkey; Biotechnology Research and Application Center, Mersin University, Mersin 33110, Turkey.
| | - Derya Yetkin
- Advanced Technology Education Research and Application Center, Mersin University, Mersin 33110, Turkey; Department of Histology and Embryology, Mersin University, Mersin 33110, Turkey
| | - Abdulcelil Yüzer
- Department of Electronics and Automation, Vocational School of Technical Sciences at Mersin Tarsus Organized Industrial Zone, Tarsus University, Mersin 33100, Turkey
| | - Kübra Demircioğlu
- Department of Natural and Mathematical Sciences, Faculty of Engineering, Tarsus University, Mersin, Turkey
| | - Mine Ince
- Department of Natural and Mathematical Sciences, Faculty of Engineering, Tarsus University, Mersin, Turkey.
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Zhu F, Wang BR, Zhu ZF, Wang SQ, Chai CX, Shang D, Li M. Photodynamic therapy: A next alternative treatment strategy for hepatocellular carcinoma? World J Gastrointest Surg 2021; 13:1523-1535. [PMID: 35070061 PMCID: PMC8727193 DOI: 10.4240/wjgs.v13.i12.1523] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/20/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Liver cancer is one of the most common cancers in the world. Of all types of liver cancer, hepatocellular carcinoma (HCC) is known to be the most frequent primary liver malignancy and has seriously compromised the health status of the general population. Locoregional thermal ablation techniques such as radiofrequency and microwave ablation, have attracted attention in clinical practice as an alternative strategy for HCC treatment. However, their aggressive thermal effect may cause undesirable complications such as hepatic decompensation, hemorrhage, bile duct injury, extrahepatic organ injuries, and skin burn. In recent years, photodynamic therapy (PDT), a gentle locoregional treatment, has attracted attention in ablation therapy for patients with superficial or luminal tumors as an alternative treatment strategy. However, some inherent defects and extrinsic factors of PDT have limited its use in clinical practice for deep-seated HCC. In this contribution, the aim is to summarize the current status and challenges of PDT in HCC treatment and provide potential strategies to overcome these deficiencies in further clinical translational practice.
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Affiliation(s)
- Feng Zhu
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Bi-Rong Wang
- Department of Breast and Thyroid Surgery, Wuhan Fourth Hospital (Puai Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zheng-Feng Zhu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Si-Qin Wang
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Chu-Xing Chai
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Dan Shang
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Min Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Photophysical Properties of Linked Zinc Phthalocyanine to Acryloyl Chloride: N-vinylpyrrolidone Copolymer. Polymers (Basel) 2021; 13:polym13244428. [PMID: 34960979 PMCID: PMC8706078 DOI: 10.3390/polym13244428] [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: 11/08/2021] [Revised: 12/03/2021] [Accepted: 12/09/2021] [Indexed: 11/16/2022] Open
Abstract
This paper focuses on the linking of zinc phthalocyanine (ZnPc) to N-vinylpyrrolidone (N-VP): acryloyl chloride (ClAC) copolymer. The synthesis of binary N-VP:ClAC copolymer was performed by the radical polymerization method and then grafted to ZnPc by the Friedel Crafts acylation reaction. We have developed a water-soluble ZnPc:ClAC:N-VP photosensitizer with a narrow absorption band at 970 nm, fluorescence at λem = 825 nm and the decay fluorescence profile with 3-decay relatively longer times of 1.2 µs, 4.6 µs, and 37 µs. The concentration-dependent dark cytotoxicity investigated in normal fibroblasts (NHDF), malignant melanoma (MeWo), adenocarcinoma (HeLa), and hepatocellular carcinoma (HepG2) cell lines incubated to increased concentrations of ZnPc:ClAC:N-VP (up to 40 μM) for 24 h in the dark show low cytotoxicity. Maximum cell viability in HeLa and HepG2 tumor cell lines was observed.
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Didamson OC, Abrahamse H. Targeted Photodynamic Diagnosis and Therapy for Esophageal Cancer: Potential Role of Functionalized Nanomedicine. Pharmaceutics 2021; 13:1943. [PMID: 34834358 PMCID: PMC8625244 DOI: 10.3390/pharmaceutics13111943] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 10/26/2021] [Accepted: 10/31/2021] [Indexed: 12/11/2022] Open
Abstract
Esophageal cancer is often diagnosed at the late stage when cancer has already spread and is characterized by a poor prognosis. Therefore, early diagnosis is vital for a better and efficient treatment outcome. Upper endoscopy with biopsy is the standard diagnostic tool for esophageal cancer but is challenging to diagnose at its premalignant stage, while conventional treatments such as surgery, chemotherapy, and irradiation therapy, are challenging to eliminate the tumor. Photodynamic diagnosis (PDD) and therapy (PDT) modalities that employ photosensitizers (PSs) are emerging diagnostic and therapeutic strategies for esophageal cancer. However, some flaws associated with the classic PSs have limited their clinical applications. Functionalized nanomedicine has emerged as a potential drug delivery system to enhance PS drug biodistribution and cellular internalization. The conjugation of PSs with functionalized nanomedicine enables increased localization within esophageal cancer cells due to improved solubility and stability in blood circulation. This review highlights PS drugs used for PDD and PDT for esophageal cancer. In addition, it focuses on the various functionalized nanomedicine explored for esophageal cancer and their role in targeted PDD and PDT for diagnosis and treatment.
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Affiliation(s)
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg 2028, South Africa;
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Gholizadeh M, Doustvandi MA, Mohammadnejad F, Shadbad MA, Tajalli H, Brunetti O, Argentiero A, Silvestris N, Baradaran B. Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers? Molecules 2021; 26:6877. [PMID: 34833970 PMCID: PMC8621355 DOI: 10.3390/molecules26226877] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 11/03/2021] [Accepted: 11/04/2021] [Indexed: 02/07/2023] Open
Abstract
Photodynamic therapy (PDT) is a light-based cancer therapy approach that has shown promising results in treating various malignancies. Growing evidence indicates that cancer stem cells (CSCs) are implicated in tumor recurrence, metastasis, and cancer therapy resistance in colorectal cancer (CRC); thus, targeting these cells can ameliorate the prognosis of affected patients. Based on our bioinformatics results, SOX2 overexpression is significantly associated with inferior disease-specific survival and worsened the progression-free interval of CRC patients. Our results demonstrate that zinc phthalocyanine (ZnPc)-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially decrease tumor migration via downregulating MMP9 and ROCK1 and inhibit the clonogenicity of SW480 cells via downregulating CD44 and SOX2. Despite inhibiting clonogenicity, ZnPc-PDT with 12 J/cm2 irradiation fails to downregulate CD44 expression in SW480 cells. Our results indicate that ZnPc-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially reduce the cell viability of SW480 cells and stimulate autophagy in the tumoral cells. Moreover, our results show that ZnPc-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially arrest the cell cycle at the sub-G1 level, stimulate the intrinsic apoptosis pathway via upregulating caspase-3 and caspase-9 and downregulating Bcl-2. Indeed, our bioinformatics results show considerable interactions between the studied CSC-related genes with the studied migration- and apoptosis-related genes. Collectively, the current study highlights the potential role of ZnPc-PDT in inhibiting stemness and CRC development, which can ameliorate the prognosis of CRC patients.
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Affiliation(s)
- Mahsa Gholizadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran; (M.G.); (M.A.D.); (F.M.); (M.A.S.)
| | - Mohammad Amin Doustvandi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran; (M.G.); (M.A.D.); (F.M.); (M.A.S.)
| | - Fateme Mohammadnejad
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran; (M.G.); (M.A.D.); (F.M.); (M.A.S.)
| | - Mahdi Abdoli Shadbad
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran; (M.G.); (M.A.D.); (F.M.); (M.A.S.)
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran
| | - Habib Tajalli
- Biophotonic Research Center, Islamic Azad University, Tabriz Branch, Tabriz 51579-44533, Iran;
- Research Institute for Applied Physics and Astronomy, University of Tabriz, Tabriz 51666-16471, Iran
| | - Oronzo Brunetti
- Istituto Tumori BariGiovanni Paolo II, Istituto Nazionale dei Tumori (IRCCS), 70124 Bari, Italy; (O.B.); (A.A.)
| | - Antonella Argentiero
- Istituto Tumori BariGiovanni Paolo II, Istituto Nazionale dei Tumori (IRCCS), 70124 Bari, Italy; (O.B.); (A.A.)
| | - Nicola Silvestris
- Istituto Tumori BariGiovanni Paolo II, Istituto Nazionale dei Tumori (IRCCS), 70124 Bari, Italy; (O.B.); (A.A.)
- Department of Biomedical Sciences and Human Oncology, School of Medicine, University of Bari Aldo Moro, 70124 Bari, Italy
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran; (M.G.); (M.A.D.); (F.M.); (M.A.S.)
- Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran
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Li L, Song D, Qi L, Jiang M, Wu Y, Gan J, Cao K, Li Y, Bai Y, Zheng T. Photodynamic therapy induces human esophageal carcinoma cell pyroptosis by targeting the PKM2/caspase-8/caspase-3/GSDME axis. Cancer Lett 2021; 520:143-159. [PMID: 34256094 DOI: 10.1016/j.canlet.2021.07.014] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/24/2021] [Accepted: 07/08/2021] [Indexed: 12/17/2022]
Abstract
Photodynamic therapy (PDT) uses a photosensitizer (PS) and visible light to induce cancer cell death. Pyroptosis is a new type of programmed cell death that is associated with the gasdermin protein family. However, the precise mechanism of pyroptosis in PDT-induced suppression of esophageal cancer remains unknown. We demonstrate that PDT can induce gasdermin E (GSDME)-mediated pyroptosis, which is characterized by the formation of pyroptotic blebs in esophageal squamous cell carcinoma (ESCC), which burst and release intracellular contents and pro-inflammatory mediators. Mechanistically, PDT may inhibit pyruvate kinase M2 (PKM2) and consequently, activate caspase-8 and caspase-3, which ultimately releases N-GSDME and triggers pyroptosis in ESCC. Moreover, PDT decreased the efficiency of pyroptosis in the presence of a glycolytic inhibitor. Overall, our results show that PDT induces pyroptosis in ESCC by targeting the PKM2/caspase-8/caspase-3/GSDME axis. This is the first in-depth study of the specific mechanism underlying PKM2-mediated pyroptosis under PDT in ESCC, and potentially has great implications for the clinical application of PDT in ESCC.
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Affiliation(s)
- Lisha Li
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China
| | - Dongfeng Song
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China
| | - Ling Qi
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China
| | - Mingxia Jiang
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China
| | - Yiming Wu
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China
| | - Junqing Gan
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China
| | - Kui Cao
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China
| | - Yanjing Li
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China.
| | - Yuxian Bai
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China.
| | - Tongsen Zheng
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150 Haping St, Nangang District, Harbin, Heilongjiang, 150081, PR China.
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12
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Pellei M, Del Bello F, Porchia M, Santini C. Zinc coordination complexes as anticancer agents. Coord Chem Rev 2021. [DOI: 10.1016/j.ccr.2021.214088] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Fraguas-Sánchez AI, Martín-Sabroso C, Torres-Suárez AI. The chick embryo chorioallantoic membrane model: a research approach for ex vivo and in vivo experiments. Curr Med Chem 2021; 29:1702-1717. [PMID: 34176455 DOI: 10.2174/0929867328666210625105438] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 05/09/2021] [Accepted: 05/11/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND The chick chorioallantoic membrane (CAM) model has attracted a great deal of interest in pharmaceutical and biological research as an alternative or complementary in vivo assay to animal models. Traditionally, CAM assay has been widely used to perform some toxicological studies, specifically to evaluate the skin, ocular and embryo toxicity of new drugs and formulations, and perform angiogenesis studies. Due to the possibility to generate the tumors onto the CAM, this model has also become an excellent strategy to evaluate the metastatic potential of different tumours and test the efficacy of novel anticancer therapies in vivo. Moreover, in the recent years, its use has considerably grown in other research areas, including the evaluation of new anti-infective agents, the development of biodistribution studies and tissue engineering research. OBJECTIVES This manuscript provides a critical overview of the use of CAM model in pharmaceutical and biological research, especially to test the toxicity of new drugs and formulations and the biodistribution and the efficacy of novel anticancer and anti-infective therapies, analyzing its advantages and disadvantages compared to animal models. CONCLUSION The chick chorioallantoic membrane model shows great utility in several research areas, such as cancer, toxicology, biodistribution studies and anti-infective therapies. In fact, it has become an intermediate stage between in vitro experiments and animal studies, and, in the case of toxicological studies (skin and ocular toxicity), has even replaced the animal models.
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Affiliation(s)
- Ana Isabel Fraguas-Sánchez
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Cristina Martín-Sabroso
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Ana Isabel Torres-Suárez
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
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14
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Senapathy GJ, George BP, Abrahamse H. Exploring the Role of Phytochemicals as Potent Natural Photosensitizers in Photodynamic Therapy. Anticancer Agents Med Chem 2021; 20:1831-1844. [PMID: 32619181 DOI: 10.2174/1871520620666200703192127] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 03/05/2020] [Accepted: 03/31/2020] [Indexed: 01/01/2023]
Abstract
BACKGROUND Cancer is still considered a deadly disease worldwide due to difficulties in diagnosis, painful treatment procedures, costly therapies, side effects, and cancer relapse. Cancer treatments using conventional methods like chemotherapy and radiotherapy were not convincing due to its post-treatment toxicity in the host. In Photodynamic Therapy (PDT), three individual non-toxic components including a photosensitizer, light source and oxygen cause damage to the cells and tissues when they are combined. OBJECTIVE In recent years, phytochemicals are being increasingly recognized as potent complementary drugs for cancer because of its natural availability, less toxicity and therapeutic efficiency in par with commercial drugs. Hence, the idea of using phytochemicals as natural photosensitizers in PDT resulted in a multiple pool of research studies with promising results in preclinical and clinical investigations. METHODS In this review, the potential of phytochemicals to act as natural photosensitizers for PDT, their mode of action, drawbacks, challenges and possible solutions are discussed in detail. RESULTS In PDT, natural photosensitizers, when used alone or in combination with other photosensitizers, induced cell death by apoptosis and necrosis, increased oxidative stress, altered cancer cell death signaling pathways, increased cytotoxicity and DNA damage in cancer cells. The pro-oxidant nature of certain antioxidant polyphenols, hormesis phenomenon, Warburg effect and DNA damaging potential plays a significant role in the photosensitizing mechanism of phytochemicals in PDT. CONCLUSION This review explores the role of phytochemicals that can act as photosensitizers alone or in combination with PDT and its mechanism of action on different cancers.
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Affiliation(s)
- Giftson J Senapathy
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa
| | - Blassan P George
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa
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15
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Gan J, Li S, Meng Y, Liao Y, Jiang M, Qi L, Li Y, Bai Y. The influence of photodynamic therapy on the Warburg effect in esophageal cancer cells. Lasers Med Sci 2020; 35:1741-1750. [PMID: 32034563 DOI: 10.1007/s10103-020-02966-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 01/13/2020] [Indexed: 12/16/2022]
Abstract
To investigate whether the Warburg effect is a key modulator on the resistance mechanism of photodynamic therapy (PDT). Glycolysis was examined by the test of lactate product and glucose uptake at different post-PDT time points. Cell viability was detected by the CCK-8 assay and cell proliferation was detected by colony formation assay. The expression of glycolysis and related proteins were examined by western blotting. Target gene was silenced by RNAi. In the present study, we assessed the effect of PDT on cancer cell glycolysis. Our team has demonstrated that pyruvate kinase M2 (PKM2), a key speed-limiting enzyme of glycolysis, was significantly overexpressed in patients with esophageal cancer. Our results in the present study showed that PKM2 was downregulated, and lactate product and glucose uptake were inhibited in cells exposed to 5-aminolevulinic acid (5-ALA)-mediated PDT at 4 h after treatment. However, at 24 h after PDT, we observed a substantial increase in PKM2 expression, lactate product, and glucose uptake. Moreover, silencing of PKM2 gene abrogated the upregulatory effect of PDT on glycolysis at late post-PDT period. 2-Deoxy-D-glucose (2-DG) is a recognized chemical inhibitor of glycolysis. The combined treatment of 2-DG and PDT significantly inhibited tumor growth in vitro at 24 h. These results demonstrate that PDT drives the Warburg effect in a time-dependent manner, and PKM2 plays an important role in this progress, which indicated that PKM2 may be a potential molecular target to increase the sensitivity of esophageal cancer cells to PDT.
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Affiliation(s)
- Junqing Gan
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Shumin Li
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Yu Meng
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Yuanyu Liao
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Mingxia Jiang
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Ling Qi
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China
| | - Yanjing Li
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China.
| | - Yuxian Bai
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China.
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Ogbodu RO, Nitzsche B, Ma A, Atilla D, Gürek AG, Höpfner M. Photodynamic therapy of hepatocellular carcinoma using tetra-triethyleneoxysulfonyl zinc phthalocyanine as photosensitizer. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2020; 208:111915. [DOI: 10.1016/j.jphotobiol.2020.111915] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 04/15/2020] [Accepted: 05/19/2020] [Indexed: 02/07/2023]
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Brozek-Pluska B, Jarota A, Kania R, Abramczyk H. Zinc Phthalocyanine Photochemistry by Raman Imaging, Fluorescence Spectroscopy and Femtosecond Spectroscopy in Normal and Cancerous Human Colon Tissues and Single Cells. Molecules 2020; 25:E2688. [PMID: 32531903 PMCID: PMC7321347 DOI: 10.3390/molecules25112688] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/08/2020] [Accepted: 06/09/2020] [Indexed: 01/01/2023] Open
Abstract
Photodynamic therapy is a clinically approved alternative method for cancer treatment in which a combination of nontoxic drugs known as photosensitizers and oxygen is used. Despite intensive investigations and encouraging results, zinc phthalocyanines (ZnPcs) have not yet been approved as photosensitizers for clinical use. Label-free Raman imaging of nonfixed and unstained normal and cancerous colon human tissues and normal human CCD18-Co and cancerous CaCo-2 cell lines, without and after adding ZnPcS4 photosensitizer, was analyzed. The biochemical composition of normal and cancerous colon tissues and colon cells without and after adding ZnPcS4 at the subcellular level was determined. Analyzing the fluorescence/Raman signals of ZnPcS4, we found that in normal human colon tissue samples, in contrast to cancerous ones, there is a lower affinity to ZnPcS4 phthalocyanine. Moreover, a higher concentration in cancerous tissue was concomitant with a blue shift of the maximum peak position specific for the photosensitizer from 691-695 nm to 689 nm. Simultaneously for both types of samples, the signal was observed in the monomer region, confirming the excellent properties of ZnPcS4 for photo therapy (PDT). For colon cell experiments with a lower concentration of ZnPcS4 photosensitizer, c = 1 × 10-6 M, the phthalocyanine was localized in mitochondria/lipid structures; for a higher concentration, c = 9 × 10-6 M, localization inside the nucleus was predominant. Based on time-resolved experiments, we found that ZnPcS4 in the presence of biological interfaces features longer excited-state lifetime photosensitizers compared to the aqueous solution and bare ZnPcS4 film on CaF2 substrate, which is beneficial for application in PDT.
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Affiliation(s)
- Beata Brozek-Pluska
- Laboratory of Laser Molecular Spectroscopy, Institute of Applied Radiation Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, Poland; (A.J.); (R.K.); (H.A.)
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Al-Bahrani HA, Kareem MM, Kadhum AA, Alrazzak NA. Synthesis and Characterization of New Zinc Phthalocyanine - Dodecenyl Succinic Anhydride Benzoic Groups. Curr Org Synth 2020; 17:488-495. [PMID: 32427085 DOI: 10.2174/1570179417666200519091950] [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: 11/24/2019] [Revised: 04/16/2020] [Accepted: 04/16/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND The phthalocyanines a series of compounds involves four iso-indole units linked by aza nitrogen atoms bonded with metal atoms that are normally located in the center a phthalocyanines ring. Some of the central metal-phthalocyanines can be excited by ultraviolet light and emit a fluorescence in far-red region. OBJECTIVE To synthesize a derivative of phthalocyanines namely 4,4',4' '-tri-(dodecenyl succinic anhydride)- 4' ' '-(5-amino salicylic acid) zinc phthalocyanine with a zinc central metal. MATERIALS AND METHODS The reaction of 4- nitro Phthalonitrile and 4- amino Phthalonitrile with ZnCl2 in the presence of dimethyl amino ethanol afforded 4,4',4' '-triamino-4' ' '-nitro zinc phthalocyanine. This product reacted with 5-amino salicylic acid to yield tetra-(5-amino salicylic acid) zinc phthalocyanine. A dodecenyl succinic anhydride was added on the amine group of benzoic rings to afford 4,4',4' '-tri-(dodecenyl succinic anhydride)-4' ' '-(5-amino salicylic acid) zinc phthalocyanine(I), the target compound. RESULTS AND DISCUSSION Compound I is successfully synthesized with a yield of 72% from tetra-(5-amino salicylic acid) zinc phthalocyanine with dodecenyl succinic anhydride. CONCLUSION The newly synthesized molecule of 4,4',4' '-tri-(dodecenyl succinic anhydride)-4' ' '-(5-amino salicylic acid) zinc phthalocyanine (I), tetra-(5-amino salicylic acid) zinc phthalocyanine(E) and 4,4',4' '- triamino-4' ' '-nitro zinc phthalocyanine (S). The reaction of 4- nitro Phthalonitrile and 4- amino and the structure of compound I is confirmed and its formation was proven.
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Affiliation(s)
| | | | | | - Nour A Alrazzak
- Departmemt of Chemistry, College of Science for Women, University of Babylon, Hilla, Iraq
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Montané X, Bajek A, Roszkowski K, Montornés JM, Giamberini M, Roszkowski S, Kowalczyk O, Garcia-Valls R, Tylkowski B. Encapsulation for Cancer Therapy. Molecules 2020; 25:E1605. [PMID: 32244513 PMCID: PMC7180689 DOI: 10.3390/molecules25071605] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 03/27/2020] [Accepted: 03/30/2020] [Indexed: 01/10/2023] Open
Abstract
The current rapid advancement of numerous nanotechnology tools is being employed in treatment of many terminal diseases such as cancer. Nanocapsules (NCs) containing an anti-cancer drug offer a very promising alternative to conventional treatments, mostly due to their targeted delivery and precise action, and thereby they can be used in distinct applications: as biosensors or in medical imaging, allowing for cancer detection as well as agents/carriers in targeted drug delivery. The possibility of using different systems-inorganic nanoparticles, dendrimers, proteins, polymeric micelles, liposomes, carbon nanotubes (CNTs), quantum dots (QDs), biopolymeric nanoparticles and their combinations-offers multiple benefits to early cancer detection as well as controlled drug delivery to specific locations. This review focused on the key and recent progress in the encapsulation of anticancer drugs that include methods of preparation, drug loading and drug release mechanism on the presented nanosystems. Furthermore, the future directions in applications of various nanoparticles are highlighted.
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Affiliation(s)
- Xavier Montané
- Department of Chemical Engineering, Universitat Rovira i Virgili, Av. Països Catalans 26, Campus Sescelades, 43007 Tarragona, Spain; (M.G.); (R.G.-V.)
| | - Anna Bajek
- Department of Tissue Engineering Chair of Urology, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, Karlowicza St. 24, 85-092 Bydgoszcz, Poland;
| | - Krzysztof Roszkowski
- Department of Oncology, Nicolaus Copernicus University, Romanowskiej St. 2, 85-796 Bydgoszcz, Poland;
| | - Josep M. Montornés
- Eurecat, Centre Tecnològic de Catalunya. Chemical Technologies Unit, Marcel·lí Domingo s/n, 43007 Tarragona, Spain;
| | - Marta Giamberini
- Department of Chemical Engineering, Universitat Rovira i Virgili, Av. Països Catalans 26, Campus Sescelades, 43007 Tarragona, Spain; (M.G.); (R.G.-V.)
| | - Szymon Roszkowski
- Faculty of Agronomy and Bioengineering, Poznan University of Life Sciences, Szydlowska St. 50, 60-656 Poznan, Poland;
| | - Oliwia Kowalczyk
- Research and Education Unit for Communication in Healthcare Department of Cardiac Surgery, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, M. Curie Sklodowskiej St. 9, 85-094 Bydgoszcz, Poland;
| | - Ricard Garcia-Valls
- Department of Chemical Engineering, Universitat Rovira i Virgili, Av. Països Catalans 26, Campus Sescelades, 43007 Tarragona, Spain; (M.G.); (R.G.-V.)
| | - Bartosz Tylkowski
- Eurecat, Centre Tecnològic de Catalunya. Chemical Technologies Unit, Marcel·lí Domingo s/n, 43007 Tarragona, Spain;
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Tang Q, Hu P, Peng H, Zhang N, Zheng Q, He Y. Near-Infrared Laser-Triggered, Self-Immolative Smart Polymersomes for in vivo Cancer Therapy. Int J Nanomedicine 2020; 15:137-149. [PMID: 32021170 PMCID: PMC6964533 DOI: 10.2147/ijn.s224502] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 11/14/2019] [Indexed: 12/24/2022] Open
Abstract
Purpose Traditional chemotherapy is accompanied by significant side effects, which, in many aspects, limits its treatment efficacy and clinical applications. Herein, we report an oxidative responsive polymersome nanosystem mediated by near infrared (NIR) light which exhibited the combination effect of photodynamic therapy (PDT) and chemotherapy. Methods In our study, poly (propylene sulfide)20-bl-poly (ethylene glycol)12 (PPS20-b-PEG12) block copolymer was synthesized and employed to prepare the polymersome. The hydrophobic photosensitizer zinc phthalocyanine (ZnPc) was loaded in the shell and the hydrophilic doxorubicin hydrochloride (DOX·HCl) in the inner aqueous space of the polymersome. Results Under the irradiation of 660 nm NIR light, singlet oxygen 1O2 molecules were generated from ZnPc to oxidize the neighbouring sulfur atoms on the PPS block which eventually ruptured the intact structure of polymersomes, leading to the release of encapsulated DOX·HCl. The released DOX and the 1O2 could achieve a combination effect for cancer therapy if the laser activation and drug release occur at the tumoral sites. In vitro studies confirmed the generation of singlet oxygen and DOX release by NIR irradiation. In vivo studies showed that such a combined PDT-chemotherapy nanosystem could accumulate in A375 tumors efficiently, thus leading to significant inhibition on tumor growth as compared to PDT (PZ group) or chemotherapy alone (DOX group). Conclusion In summary, this oxidation-sensitive nanosystem showed excellent anti-tumor effects by synergistic chemophotodynamic therapy, indicating that this novel drug delivery strategy could potentially provide a new means for cancer treatments in clinic.
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Affiliation(s)
- Qing Tang
- School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, People's Republic of China
| | - Ping Hu
- School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, People's Republic of China.,School of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China
| | - Haibo Peng
- School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, People's Republic of China
| | - Ning Zhang
- School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, People's Republic of China
| | - Qiang Zheng
- School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, People's Republic of China
| | - Yun He
- School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, People's Republic of China
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Tunç G, Albakour M, Ahsen V, Gürek AG. Peripherally carboxylic acid substituted asymmetric zinc(II) phthalocyanines: Synthesis and photophysicochemical properties. J PORPHYR PHTHALOCYA 2020. [DOI: 10.1142/s1088424619501402] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Four asymmetric Zn(II) phthalocyanines (Pc1–Pc4) bearing a carboxylic acid group in the peripheral position have been designed and synthesized to investigate the influence of the distance between COOH group and the phthalocyanine core on their photophysical and photochemical properties. The novel phthalocyanine complexes were characterized by [Formula: see text]H, [Formula: see text]C NMR, IR, and UV-vis spectroscopies, elemental analysis and matrix-assisted laser desorption ionization mass spectrometry (MALDI). The aggregation behavior, photophysical and photochemical properties such as fluorescence lifetime and quantum yields and singlet oxygen quantum yields of Pc1–Pc4 were explored in tetrahydrofuran (THF) to the determination of the potential use of these novel phthalocyanines as photosensitizers for different applications such as photovoltaic technologies and photodynamic therapy (PDT). Pc1–Pc4exhibited high singlet oxygen generation quantum yields (0.84, 0.66, 0.88 and 0.65, respectively). Fluorescence quantum yields could be obtained for Pc1, Pc2, Pc3 and Pc4 (0.13, 0.31, 0.10 and 0.25, respectively) in THF.
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Affiliation(s)
- Gülenay Tunç
- Department of Chemistry, Gebze Technical University, 41400, Gebze, Kocaeli, Turkey
| | - Mohamad Albakour
- Department of Chemistry, Gebze Technical University, 41400, Gebze, Kocaeli, Turkey
| | - Vefa Ahsen
- Department of Chemistry, Gebze Technical University, 41400, Gebze, Kocaeli, Turkey
| | - Ayşe Gül Gürek
- Department of Chemistry, Gebze Technical University, 41400, Gebze, Kocaeli, Turkey
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Lopes TZ, de Moraes FR, Tedesco AC, Arni RK, Rahal P, Calmon MF. Berberine associated photodynamic therapy promotes autophagy and apoptosis via ROS generation in renal carcinoma cells. Biomed Pharmacother 2019; 123:109794. [PMID: 31874443 DOI: 10.1016/j.biopha.2019.109794] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 12/05/2019] [Accepted: 12/10/2019] [Indexed: 12/12/2022] Open
Abstract
Renal cell carcinoma (RCC) consists of the most lethal common urological cancer and the clinical practice has shown that resistant RCC to commons therapies is extremely high. Berberine is an isoquinoline alkaloid, presents in different kinds of plants and it has long been used in Chinese medicine. It has several properties, such as antioxidant, anti-inflammatory, anti-diabetic, anti-microbial and anti-cancer. Moreover, berberine has photosensitive characteristics and its association with photodynamic therapy (PDT) is effective against tumor cells. This study aimed to evaluate the effects of berberine associated with PDT in renal carcinoma cell lines. The cellular viability assay showed increased cytotoxicity in concentration and time-dependent manner. Berberine presented efficient internalization in all cell lines analyzed. In addition, after treatment with berberine associated with PDT, it was observed a high phototoxicity effect with less than 20 % of viable cells. In this study we observed that the increase of reactive oxygen species (ROS) levels was accompanied by an increase of autophagy levels and apoptosis by caspase 3 activity, suggesting cell death by both mechanisms. Additionally, three target genes of anti-cancer drugs were differentially expressed in 786-O cells, being that Vascular Endothelial Growth Factor-D (FIGF) and Human Telomerase Reverse Transcriptase (TERT) gene presented low expression and Polo Like Kinase 3 (PLK3) presented overexpression after treatment with berberine associated with PDT. In this study, the proposed treatment triggered metabolites changes related to cell proliferation, tumorigenesis and angiogenesis. Thus, it was possible to suggest that berberine has promising potential as a photosensitizing agent in a photodynamic therapy, because it induced significant anticancer effects on renal carcinoma cells.
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Affiliation(s)
- Tairine Zara Lopes
- Laboratory of Genomics Studies, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
| | - Fabio Rogério de Moraes
- Physics Department, São Paulo State University, São José do Rio Preto, São Paulo, Brazil; Multiuser Center for Biomolecular Innovation, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
| | - Antonio Claudio Tedesco
- Department of Chemistry, Center of Nanotechnology and Tissue Engineering-Photobiology and Photomedicine Research Group, Faculty of Philosophy, Sciences and Letters of Ribeirao Preto, University of São Paulo, Ribeirao Preto, SP, Brazil
| | - Raghuvir Krishnaswamy Arni
- Physics Department, São Paulo State University, São José do Rio Preto, São Paulo, Brazil; Multiuser Center for Biomolecular Innovation, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
| | - Paula Rahal
- Laboratory of Genomics Studies, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
| | - Marilia Freitas Calmon
- Laboratory of Genomics Studies, São Paulo State University, São José do Rio Preto, São Paulo, Brazil.
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Naidoo C, Kruger CA, Abrahamse H. Targeted photodynamic therapy treatment of in vitro A375 metastatic melanoma cells. Oncotarget 2019; 10:6079-6095. [PMID: 31692760 PMCID: PMC6817449 DOI: 10.18632/oncotarget.27221] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 08/17/2019] [Indexed: 12/13/2022] Open
Abstract
Metastatic Melanoma (MM) is a deadly form of skin cancer and many photodynamic therapy (PDT) studies have noted limitations in relation to effective photosensitizer (PS) drug uptake in tumors. The focus of this study was to develop a PS multicomponent nanoparticle drug conjugate carrier system which specifically targets MM cells via biomarkers to actively enhance PS delivery and so improve MM PDT. An antibody-metallated phthalocyanine-polyethylene glycol-gold nanoparticle drug conjugate, was successfully synthesized and characterized. PS active drug targeting PDT experiments at 673 nm were conducted within in vitro cultured MM. Results noted that this drug conjugate enhanced the PDT treatment of MM, through improved subcellular localization of the PS, as well as noted significantly improved cytotoxic and late apoptotic cellular death in cells. The results from this study demonstrate that through the bio-active antibody PS drug targeting of MM, the efficacy of PDT treatment for this cancer can be enhanced.
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Affiliation(s)
- Channay Naidoo
- Laser Research Centre, University of Johannesburg, Johannesburg, South Africa
| | - Cherie Ann Kruger
- Laser Research Centre, University of Johannesburg, Johannesburg, South Africa
| | - Heidi Abrahamse
- Laser Research Centre, University of Johannesburg, Johannesburg, South Africa
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24
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Li T, Lv H, Yang L, Xie J, Liu C, Xu P, Li W, Wang S, Yang D, Wu T, Yan J, Luo F. Pharmacokinetics and Tissue Distribution of DVDMS-2 in Tumor-bearing Mice. Photochem Photobiol 2019; 96:148-155. [PMID: 31574562 DOI: 10.1111/php.13171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Accepted: 09/26/2019] [Indexed: 01/10/2023]
Abstract
DVDMS-2 is a novel candidate for photodynamic therapy of tumors. The purpose of the present study was to assess the distribution and elimination of DVDMS-2 in mice bearing hepatoma 22 tumors. DVDMS-2 (1, 2 and 4 mg kg-1 ) was injected intravenously into the mice, extracted from biological tissues and quantified using a fluorescence assay. The data obtained were processed with WinNonlin pharmacokinetic software. The fluorescence assay established for DVDMS-2 quantification was a rapid, reproducible, sensitive and specific method with good linearity. The pharmacokinetics of DVDMS-2 in tumor-bearing mice conformed to a two-compartment model. DVDMS-2 accumulated in tumor tissue to a greater extent than adjacent tissues (skin, muscle) and sustained a relatively high-level concentration 12 to 24 h following administration, which may be the optimal treatment time point. In conclusion, DVDMS-2 selectively accumulated in tumor tissue and was eliminated at a rapid rate in tumor-bearing mice, suggesting that DVDMS-2 may have few side effects, including skin phototoxicity. The present study established the pharmacokinetic characteristics of DVDMS-2, which may be beneficial in future clinical study.
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Affiliation(s)
- Tingting Li
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Haiyan Lv
- Xiamen Mental Health Center, Xiamen Xianyue Hospital, Xiamen, Fujian, China
| | - Liu Yang
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Jun Xie
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Cong Liu
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Peilan Xu
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Wanyun Li
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Shengyu Wang
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Dong Yang
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Ting Wu
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Jianghua Yan
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Fanghong Luo
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China
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25
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Olek M, Kasperski J, Skaba D, Wiench R, Cieślar G, Kawczyk-Krupka A. Photodynamic therapy for the treatment of oral squamous carcinoma—Clinical implications resulting from in vitro research. Photodiagnosis Photodyn Ther 2019; 27:255-267. [DOI: 10.1016/j.pdpdt.2019.06.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 06/16/2019] [Accepted: 06/17/2019] [Indexed: 12/27/2022]
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26
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Zinc(II) phthalocyanines as photosensitizers for antitumor photodynamic therapy. Int J Biochem Cell Biol 2019; 114:105575. [PMID: 31362060 DOI: 10.1016/j.biocel.2019.105575] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 07/18/2019] [Accepted: 07/22/2019] [Indexed: 12/31/2022]
Abstract
Photodynamic therapy (PDT) is a highly specific and clinically approved method for cancer treatment in which a nontoxic drug known as photosensitizer (PS) is administered to a patient. After selective tumor irradiation, an almost complete eradication of the tumor can be reached as a consequence of reactive oxygen species (ROS) generation, which not only damage tumor cells, but also lead to tumor-associated vasculature occlusion and the induction of an immune response. Despite exhaustive investigation and encouraging results, zinc(II) phthalocyanines (ZnPcs) have not been approved as PSs for clinical use yet. This review presents an overview on the physicochemical properties of ZnPcs and biological results obtained both in vitro and in more complex models, such as 3D cell cultures, chicken chorioallantoic membranes and tumor-bearing mice. Cell death pathways induced after PDT treatment with ZnPcs are discussed in each case. Finally, combined therapeutic strategies including ZnPcs and the currently available clinical trials are mentioned.
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27
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Nene LC, Managa ME, Oluwole DO, Mafukidze DM, Sindelo A, Nyokong T. The photo-physicochemical properties and in vitro photodynamic therapy activity of differently substituted-zinc (II)-phthalocyanines and graphene quantum dots conjugates on MCF7 breast cancer cell line. Inorganica Chim Acta 2019. [DOI: 10.1016/j.ica.2019.01.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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28
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Keyal U, Luo Q, Bhatta AK, Luan H, Zhang P, Wu Q, Zhang H, Liu P, Zhang L, Wang P, Yang D, Zhang G, Yao J, Wang X, Shi L. Zinc pthalocyanine-loaded chitosan/mPEG-PLA nanoparticles-mediated photodynamic therapy for the treatment of cutaneous squamous cell carcinoma. JOURNAL OF BIOPHOTONICS 2018; 11:e201800114. [PMID: 29893047 DOI: 10.1002/jbio.201800114] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 06/11/2018] [Indexed: 06/08/2023]
Abstract
Zinc pthalocyanine (ZnPc) is a second-generation photodynamic therapy (PDT) sensitizer with sufficient PDT activity for squamous cell carcinoma (SCC). ZnPc is hydrophobic and insoluble in water, which creates hurdles in systemic administration and hence restricts its use in clinic. Here we have loaded ZnPc on chitosan/methoxy polyethylene glycol-polylactic acid (CPP) nanoparticles to form Z-CPP to enhance PDT efficacy. In vitro and in vivo studies were performed to see dark toxicity of the compounds ZnPc, CPP and Z-CPP. Then PDT was done and its growth inhibitory effect on SCC cells was evaluated. In addition, reactive oxygen species (ROS) formation and apoptosis of cancer cells following PDT were studied. The results showed that the tested compounds exhibit no dark toxicity and the effect of PDT was significantly better with Z-CPP when compared to free ZnPc (P < .05). Photoactivation of Z-CPP led to a dose-dependent growth inhibition of cancer cells of >50% at 1 μM to >80% at 10 μM concentration. Also Z-CPP-treated cells had highest number of apoptotic cells and produced more ROS compared to free ZnPc-treated cells (P < .05). Hence, this study suggests that Z-CPP is a suitable pharmaceutical compound to increase PDT efficacy.
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Affiliation(s)
- Uma Keyal
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Qiong Luo
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Shanghai, P. R. China
| | - Anil K Bhatta
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Hansen Luan
- National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, P. R. China
| | - Ping Zhang
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, P. R. China
| | - Qianqian Wu
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Haiyan Zhang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Pei Liu
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Linglin Zhang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Peiru Wang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Degang Yang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Guolong Zhang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Jing Yao
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, P. R. China
| | - Xiuli Wang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
| | - Lei Shi
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China
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29
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Gvozdev DA, Maksimov EG, Strakhovskaya MG, Moysenovich AM, Ramonova AA, Moisenovich MM, Goryachev SN, Paschenko VZ, Rubin AB. A CdSe/ZnS quantum dot-based platform for the delivery of aluminum phthalocyanines to bacterial cells. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2018; 187:170-179. [PMID: 30170287 DOI: 10.1016/j.jphotobiol.2018.08.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 07/18/2018] [Accepted: 08/01/2018] [Indexed: 01/08/2023]
Abstract
Enhancement of optical properties of photosensitizers by additional light-harvesting antennas is promising for the improvement of the photodynamic therapy. However, large number of parameters determine interactions of nanoparticles and photosensitizers in complex and, thus the photodynamic efficacy of the hybrid structure. In order to achieve high efficiency of energetic coupling and photodynamic activity of such complexes it is important to know the location of the photosensitizer molecule on the nanoparticle, because it affects the spectral properties of the photosensitizer and the stability of the hybrid complex in vitro/in vivo. In this work complexes of polycationic aluminum phthalocyanines and CdSe/ZnS quantum dots were obtained. We used quantum dots which outer shell consists of polymer with carboxyl groups and provides water solubility and the negative charge of the nanoparticle. We found that phthalocyanine molecules could penetrate deeply into the polymer shell of quantum dot, leading thereby to significant changes in the spectral and photodynamic properties of phthalocyanines. We also showed that noncovalent interactions between phthalocyanine and quantum dot provide possibility for a release of the phthalocyanine from the hybrid complex and its binding to both Gram-positive and Gram-negative bacterial cells. Also, detailed characterization of the nanoparticle core and shell sizes was carried out.
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Affiliation(s)
- D A Gvozdev
- Department of Biophysics, Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia.
| | - E G Maksimov
- Department of Biophysics, Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia
| | - M G Strakhovskaya
- Department of Biophysics, Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia; Federal Scientific and Clinical Center for Specialized Medical Service and Medical Technologies, FMBA, Moscow, Russia
| | - A M Moysenovich
- Department of Biophysics, Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia
| | - A A Ramonova
- Department of Biophysics, Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia
| | - M M Moisenovich
- Department of Biophysics, Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia
| | - S N Goryachev
- Department of Biophysics, Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia
| | - V Z Paschenko
- Department of Biophysics, Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia
| | - A B Rubin
- Department of Biophysics, Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia
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30
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Schmidt J, Kuzyniak W, Berkholz J, Steinemann G, Ogbodu R, Hoffmann B, Nouailles G, Gürek AG, Nitzsche B, Höpfner M. Novel zinc‑ and silicon‑phthalocyanines as photosensitizers for photodynamic therapy of cholangiocarcinoma. Int J Mol Med 2018; 42:534-546. [PMID: 29693115 DOI: 10.3892/ijmm.2018.3620] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 03/09/2018] [Indexed: 11/05/2022] Open
Abstract
Photodynamic therapy (PDT) has emerged as an effective and minimally invasive cancer treatment modality. In the present study, two novel phthalocyanines, tetra‑triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) and dihydroxy‑2,9(10),16(17),23(24)‑tetrakis(4,7,10‑trioxaundecan‑1‑sulfonyl) silicon phthalocyanine (Pc32), were investigated as photosensitizers (PS) for PDT of cholangiocarcinoma (CC). ZnPc showed a pronounced dose‑dependent and predominantly cytoplasmic accumulation in EGI‑1 and TFK‑1 CC cell lines. Pc32 also accumulated in the CC cells, but this was less pronounced. Without photoactivation, the PS did not exhibit any antiproliferative or cytotoxic effects. Upon photoactivation, ZnPc induced the formation of reactive oxygen species (ROS) and immediate phototoxicity, leading to a dose‑dependent decrease in cell proliferation, and an induction of mitochondria‑driven apoptosis and cell cycle arrest of EGI‑1 and TFK‑1 cells. Although photoactivated Pc32 also induced ROS formation in the two cell lines, the extent was less marked, compared with that induced by ZnPc‑PDT, and pronounced antipoliferative effects occurred only in the less differentiated EGI‑1 cells, whereas the more differentiated TFK‑1 cells did not show sustained growth inhibition upon Pc32‑PDT induction. In vivo examinations on the antiangiogenic potency of the novel PS were performed using chorioallantoic membrane (CAM) assays, which revealed reduced angiogenic sprouting with a concomitant increase in nonperfused regions and degeneration of the vascular network of the CAM following induction with ZnPc‑PDT only. The study demonstrated the pronounced antiproliferative and antiangiogenic potency of ZnPc as a novel PS for PDT, meriting further elucidation as a promising PS for the photodynamic treatment of CC.
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Affiliation(s)
- Jacob Schmidt
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Weronika Kuzyniak
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Janine Berkholz
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Gustav Steinemann
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Racheal Ogbodu
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Björn Hoffmann
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Geraldine Nouailles
- Department of Infectious Diseases and Pulmonary Medicine, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Ayşe Gül Gürek
- Department of Chemistry, Gebze Technical University, Gebze, Kocaeli 41400, Turkey
| | - Bianca Nitzsche
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Michael Höpfner
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
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31
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Di Bari I, Granata G, Consoli GML, Sortino S. Simultaneous supramolecular activation of NO photodonor/photosensitizer ensembles by a calix[4]arene nanoreactor. NEW J CHEM 2018. [DOI: 10.1039/c8nj03704c] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
A calix[4]arene-based micellar nanoscaffold allows the co-encapsulation of photosensitizers with a NO photodonor, activating their response to light, otherwise precluded/limited in water medium, resulting in the simultaneous photogeneration of cytotoxic 1O2 and NO.
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Affiliation(s)
- Ivana Di Bari
- Laboratory of Photochemistry
- Department of Drug Science
- Catania
- Italy
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32
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Tao Y, Ou Y, Yin H, Chen Y, Zhong S, Gao Y, Zhao Z, He B, Huang Q, Deng Q. Establishment and characterization of human osteosarcoma cells resistant to pyropheophorbide-α methyl ester-mediated photodynamic therapy. Int J Oncol 2017; 51:1427-1438. [PMID: 29048645 PMCID: PMC5642392 DOI: 10.3892/ijo.2017.4136] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 09/08/2017] [Indexed: 12/20/2022] Open
Abstract
The present study was performed to establish and characterize new human osteosarcoma cell lines resistant to pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT). MPPa-PDT-resistant cells are isolated from the human osteosarcoma MG63 and HOS cell lines and two resistant populations were finally acquired, including MG63/PDT and HOS/PDT. Cell Counting Kit-8 (CCK-8) assay was used to determine the MPPa-PDT, cisplatin (CDDP) resistance and proliferation of MG63, MG63/PDT, HOS and HOS/PDT cells. The intracellular ROS were analyzed using DCFH-DA staining. The colony formation, invasion and migration of parental and resistant cells were compared. FCM was employed to examine the cell cycle distribution, the apoptosis rate and the proportion of CD133+ cells. The fluorescence intensity of intracellular MPPa was observed by fluorescence microscopy and quantified using microplate reader. The protein levels were assessed by western blotting (WB). Compared with two parental cells, MG63/PDT and HOS/PDT were 1.67- and 1.61-fold resistant to MPPa-PDT, respectively, and also exhibited the resistance to CDDP. FCM assays confirmed that both MG63/PDT and HOS/PDT cells treated with MPPa-PDT displayed a significantly lower apoptosis rate in comparison with their corresponding parental cells. The expression of apoptosis-related proteins (i.e. cleaved-caspase 3 and cleaved-PARP), intracellular ROS and the antioxidant proteins (HO-1 and SOD1) in MG63/PDT and HOS/PDT cells was also lower than that in parental cells. Both MG63/PDT and HOS/PDT cells exhibited changes in proliferation, photosensitizer absorption, colony formation, invasion, migration and the cell cycle distribution as compared to MG63 and HOS cells, respectively. Compared to MG63 and HOS cells, both resistant cell lines had a higher expression of CD133, survivin, Bcl-xL, Bcl-2, MRP1, MDR1 and ABCG2, but a lower expression of Bax. The present study successfully established two resistant human osteosarcoma cell lines which are valuable to explore the resistance-related mechanisms and the approaches to overcome resistance.
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Affiliation(s)
- Yong Tao
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
| | - Yunsheng Ou
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
| | - Hang Yin
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
| | - Yanyang Chen
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
| | - Shenxi Zhong
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
| | - Yongjian Gao
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
| | - Zenghui Zhao
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
| | - Bin He
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
| | - Qiu Huang
- Department of Orthopedics, People's Hosipital of Leshan, Leshan, Sichuan 614000, P.R. China
| | - Qianxing Deng
- Department of Orthopedics, People's Hospital of Fengdu, Fengdu, Chongqing 408200, P.R. China
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Koç V, Topal SZ, Aydın Tekdaş D, Ateş ÖD, Önal E, Dumoulin F, Gürek AG, Ahsen V. Assessment of the relevance of GaPc substituted with azido-polyethylene glycol chains for photodynamic therapy. Design, synthetic strategy, fluorescence, singlet oxygen generation, and pH-dependent spectroscopic behaviour. NEW J CHEM 2017. [DOI: 10.1039/c7nj01390f] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
New synthetic route and PDT potential of symmetrically and asymmetrically substituted Ga(iii)Pcs with terminal azides.
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Affiliation(s)
- Veysel Koç
- Gebze Technical University
- Department of Chemistry
- Gebze
- Turkey
| | | | | | | | - Emel Önal
- Gebze Technical University
- Department of Chemistry
- Gebze
- Turkey
| | | | - Ayşe Gül Gürek
- Gebze Technical University
- Department of Chemistry
- Gebze
- Turkey
| | - Vefa Ahsen
- Gebze Technical University
- Department of Chemistry
- Gebze
- Turkey
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