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Wang Z, Nie S, Wang M, Niu H, Wei L, Yang Z, Liu X, Chen Y, Yang Y, Li C, Zhang Q, Feng L, Ma H, Chen R, Cheng Y. An oxygen-independent therapeutic nanosystem for fighting against hypoxic and antioxidant microenvironment of tumor. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2025; 268:113184. [PMID: 40409132 DOI: 10.1016/j.jphotobiol.2025.113184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2025] [Revised: 05/08/2025] [Accepted: 05/17/2025] [Indexed: 05/25/2025]
Abstract
The innate hypoxic and antioxidant defendant microenvironment are the main obstacles for improving reactive oxygen species (ROS) based therapeutic efficacy against cancer. Herein, bismuth tungstate (BWO) nanoparticles (NPs) were fabricated for ultrasound activated hydroxyl radical (OH•) production through being reacted with water in an oxygen-independent manner due to their more positive potential of valent band position than that of OH• generation. For relieving antioxidant defense, BWOST NPs were designed through loading L-buthionine sulfoximine into hollow BWO NPs to inhibit the synthesis of glutathione (GSH), and coating pH-responsive tannic acid-Fe complex on the surface to prevent drug leakage. Both in vitro and in vivo assessments demonstrated that BWOST NPs could effectively lower intracellular GSH levels, inducing apoptosis of cancer cells and eliminating tumors. Therefore, BWOST NPs showed an amplified sonodynamic therapy efficacy through lower antioxidant defense and oxygen-independent OH• generation, which provided an effective strategy for improving ROS based cancer therapy.
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Affiliation(s)
- Zixuan Wang
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Shuwei Nie
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Manru Wang
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Huina Niu
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Liqi Wei
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Zhiqi Yang
- Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, College of Life Science, Jilin Agricultural University, Changchun 130118, China
| | - Xin Liu
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Yining Chen
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Yunan Yang
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Chunjiang Li
- Jilin Huaen Biotechnology Co. Ltd., Changchun 130000, China
| | - Qin Zhang
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Lina Feng
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China
| | - Hongxia Ma
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China.
| | - Rui Chen
- Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, College of Life Science, Jilin Agricultural University, Changchun 130118, China.
| | - Yan Cheng
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun 130022, China.
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Chen X, Chen C, Li Z, Liu C, Lin Z. Punicalagin as an Artemis inhibitor synergizes with photodynamic therapy in tumor suppression. Bioorg Chem 2025; 157:108282. [PMID: 39970756 DOI: 10.1016/j.bioorg.2025.108282] [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: 12/10/2024] [Revised: 01/22/2025] [Accepted: 02/13/2025] [Indexed: 02/21/2025]
Abstract
Photodynamic therapy (PDT) is a minimally invasive treatment that utilizes a photosensitizer, specific light wavelengths, and oxygen to generate reactive oxygen species (ROS), causing oxidative damage and tumor cell death. However, the effectiveness of PDT can be reduced by the intrinsic antioxidant and DNA repair mechanisms of tumor cells. Artemis (SNM1C/DCLRE1C) is an endonuclease essential for repairing DNA double-strand breaks (DSBs) via non-homologous end-joining (NHEJ). Herein, we conducted a high-throughput small-molecule screening and identified Punicalagin (PUG), a natural polyphenol from pomegranate, as a novel Artemis inhibitor with an IC50 value of 296.1 nM. We also investigated the effects of PUG combined with PDT in tumor treatment, using the pentalysine β-carbonylphthalocyanine zinc (ZnPc5K) as the photosensitizer. In HeLa cells, ZnPc5K-based PDT induced significant DSBs, which could be repaired by the intrinsic DNA repair mechanisms within 12 h. Co-treatment with PUG compromised DNA repair, promoted cell apoptosis, inhibited cell invasion, and suppressed the growth of various tumor cells. Furthermore, in a mouse xenograft model, the combination of PUG and ZnPc5K-PDT effectively inhibited tumor growth with minimal side effects. These findings suggest that PUG, as an Artemis inhibitor, can enhance the therapeutic efficacy of PDT in tumor suppression by impairing DNA repair through the NHEJ pathway.
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Affiliation(s)
- Xuening Chen
- College of Chemistry, Fuzhou University, Fuzhou, China
| | - Changkun Chen
- College of Chemistry, Fuzhou University, Fuzhou, China
| | - Zuoan Li
- Shengli Clinical Medical College of Fujian Medical University, Department of Emergency, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Key Laboratory of Emergency Medicine, Fuzhou, China
| | - Chun Liu
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, China
| | - Zhonghui Lin
- College of Chemistry, Fuzhou University, Fuzhou, China.
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3
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Consoli V, Sorrenti V, Gulisano M, Spampinato M, Vanella L. Navigating heme pathways: the breach of heme oxygenase and hemin in breast cancer. Mol Cell Biochem 2025; 480:1495-1518. [PMID: 39287890 PMCID: PMC11842487 DOI: 10.1007/s11010-024-05119-5] [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: 08/06/2024] [Accepted: 09/07/2024] [Indexed: 09/19/2024]
Abstract
Breast cancer remains a significant global health challenge, with diverse subtypes and complex molecular mechanisms underlying its development and progression. This review comprehensively examines recent advances in breast cancer research, with a focus on classification, molecular pathways, and the role of heme oxygenases (HO), heme metabolism implications, and therapeutic innovations. The classification of breast cancer subtypes based on molecular profiling has significantly improved diagnosis and treatment strategies, allowing for tailored approaches to patient care. Molecular studies have elucidated key signaling pathways and biomarkers implicated in breast cancer pathogenesis, shedding light on potential targets for therapeutic intervention. Notably, emerging evidence suggests a critical role for heme oxygenases, particularly HO-1, in breast cancer progression and therapeutic resistance, highlighting the importance of understanding heme metabolism in cancer biology. Furthermore, this review highlights recent advances in breast cancer therapy, including targeted therapies, immunotherapy, and novel drug delivery systems. Understanding the complex interplay between breast cancer subtypes, molecular pathways, and innovative therapeutic approaches is essential for improving patient outcomes and developing more effective treatment strategies in the fight against breast cancer.
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Affiliation(s)
- Valeria Consoli
- Department of Drug and Health Sciences, University of Catania, 95125, Catania, Italy
- CERNUT - Research Centre on Nutraceuticals and Health Products, University of Catania, 95125, Catania, Italy
| | - Valeria Sorrenti
- Department of Drug and Health Sciences, University of Catania, 95125, Catania, Italy
- CERNUT - Research Centre on Nutraceuticals and Health Products, University of Catania, 95125, Catania, Italy
| | - Maria Gulisano
- Department of Drug and Health Sciences, University of Catania, 95125, Catania, Italy
| | - Mariarita Spampinato
- Department of Drug and Health Sciences, University of Catania, 95125, Catania, Italy
| | - Luca Vanella
- Department of Drug and Health Sciences, University of Catania, 95125, Catania, Italy.
- CERNUT - Research Centre on Nutraceuticals and Health Products, University of Catania, 95125, Catania, Italy.
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Zhang Y, Li Z, Zhang C, Shao C, Duan Y, Zheng G, Cai Y, Ge M, Xu J. Recent advances of photodiagnosis and treatment for head and neck squamous cell carcinoma. Neoplasia 2025; 60:101118. [PMID: 39721461 PMCID: PMC11732236 DOI: 10.1016/j.neo.2024.101118] [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: 04/25/2024] [Accepted: 12/19/2024] [Indexed: 12/28/2024]
Abstract
Head and neck squamous cell carcinoma (HNSCC) are the most common type of head and neck tumor that severely threatens human health due to its highly aggressive nature and susceptibility to distant metastasis. The diagnosis of HNSCC currently relies on biopsy and histopathological examination of suspicious lesions. However, the early mucosal changes are subtle and difficult to detect by conventional oral examination. As for treatment, surgery is still the primary treatment modality. Due to the complex anatomy and the lack of intraoperative modalities to accurately determine the incision margins, surgeons are in a dilemma between extensive tumor removal and improving the quality of patient survival. As more knowledge is gained about HNSCC, the increasing recognition of the value of optical imaging has been emphasized. Optical technology offers distinctive possibilities for early preoperative diagnosis, intraoperative real-time visualization of tumor margins, sentinel lymph node biopsies, phototherapy. Fluorescence imaging, narrow-band imaging, Raman spectroscopy, optical coherence tomography, hyperspectral imaging, and photoacoustic imaging have been reported for imaging HNSCC. This article provides a comprehensive overview of the fundamental principles and clinical applications of optical imaging in the diagnosis and treatment of HNSCC, focusing on identifying its strengths and limitations to facilitate advancements in this field.
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Affiliation(s)
- Yining Zhang
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Zhenfang Li
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
| | - Chengchi Zhang
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China; Zhejiang University of Technology, Hangzhou 310023, China
| | - Chengying Shao
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Yanting Duan
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Hangzhou 310014, China; Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Hangzhou 310014, China
| | - Guowan Zheng
- Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Hangzhou 310014, China; Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Hangzhou 310014, China
| | - Yu Cai
- Department of Rehabilitation Medicine, Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
| | - Minghua Ge
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China; Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Hangzhou 310014, China; Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Hangzhou 310014, China.
| | - Jiajie Xu
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China; Zhejiang Provincial Clinical Research Center for Head & Neck Cancer, Hangzhou 310014, China; Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Hangzhou 310014, China.
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Spring BQ, Watanabe K, Ichikawa M, Mallidi S, Matsudaira T, Timerman D, Swain JWR, Mai Z, Wakimoto H, Hasan T. Red light-activated depletion of drug-refractory glioblastoma stem cells and chemosensitization of an acquired-resistant mesenchymal phenotype. Photochem Photobiol 2025; 101:215-229. [PMID: 38922889 PMCID: PMC11664018 DOI: 10.1111/php.13985] [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: 05/08/2024] [Accepted: 06/09/2024] [Indexed: 06/28/2024]
Abstract
Glioblastoma stem cells (GSCs) are potent tumor initiators resistant to radiochemotherapy, and this subpopulation is hypothesized to re-populate the tumor milieu due to selection following conventional therapies. Here, we show that 5-aminolevulinic acid (ALA) treatment-a pro-fluorophore used for fluorescence-guided cancer surgery-leads to elevated levels of fluorophore conversion in patient-derived GSC cultures, and subsequent red light-activation induces apoptosis in both intrinsically temozolomide chemotherapy-sensitive and -resistant GSC phenotypes. Red light irradiation of ALA-treated cultures also exhibits the ability to target mesenchymal GSCs (Mes-GSCs) with induced temozolomide resistance. Furthermore, sub-lethal light doses restore Mes-GSC sensitivity to temozolomide, abrogating GSC-acquired chemoresistance. These results suggest that ALA is not only useful for fluorescence-guided glioblastoma tumor resection, but that it also facilitates a GSC drug-resistance agnostic, red light-activated modality to mop up the surgical margins and prime subsequent chemotherapy.
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Affiliation(s)
- Bryan Q. Spring
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Department of Physics, Northeastern University, Boston, MA 02115, USA
| | - Kohei Watanabe
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Healthcare Optics Research Laboratory, Canon USA, Inc., Cambridge MA 02139, USA
| | - Megumi Ichikawa
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Srivalleesha Mallidi
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - Tatsuyuki Matsudaira
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Dmitriy Timerman
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Joseph W. R. Swain
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Zhiming Mai
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Hiroaki Wakimoto
- Brain Tumor Research Center and Molecular Neurosurgery Laboratory, Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Clementi R, Vargas MA, Cid M, Salvatierra N, Comín R, Tempesti T. Biocompatible Zn-Phthalocyanine/Gelatin Nanofiber Membrane for Antibacterial Therapy. Macromol Biosci 2025; 25:e2400334. [PMID: 39470704 DOI: 10.1002/mabi.202400334] [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: 07/12/2024] [Revised: 10/01/2024] [Indexed: 10/30/2024]
Abstract
In this study, the fabrication and characterization of Zn-phthalocyanine/gelatin nanofibrous membranes is reported using the electrospinning technique. The membranes exhibit a homogeneous distribution of Zn-phthalocyanine within the gelatin matrix, maintaining the structural integrity and photosensitizing properties of the phthalocyanine. Scanning electron microscopy revealed that the electrospun fibers possess diameters ranging results as 100-300, 200-700, and 300-800 nm for Gel, ZnPc/Gel 1, and ZnPc/Gel 2, respectively. The addition of ZnPc does not decrease the hydrophilicity of the Gel membrane. The nanofibrous membranes showed good cytocompatibility, as indicated by the high viability of Vero cells exposed to membrane extracts. Furthermore, these composites supported cell adhesion and proliferation on their surfaces. The two Zn-phthalocyanine/gelatin nanofiber formulations exhibited significant antimicrobial activity toward Escherichia Coli (E. Coli) and Staphylococcus Aureus (S. Aureus) under visible light illumination, achieving reductions of 3.4 log10 and 3.6 log10 CFU mL-1 for E. coli, and 3.9 log10 and 4.1 log10 CFU mL-1 for S. aureus. These results demonstrate the potential of Zn-phthalocyanine/gelatin nanofibrous membranes as effective agents in antibacterial photodynamic therapy, providing a promising solution to control bacterial infections and antibiotic resistance.
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Affiliation(s)
- Romina Clementi
- Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, X5000HUA, Argentina
| | - Maria Angela Vargas
- Laboratorio de Microbiología, Hospital Provincial Florencio Diaz, Córdoba, Argentina
| | - Mariana Cid
- Facultad Ciencias Exactas, Físicas y Naturales, Departamento de Química, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, Córdoba, 5016, Argentina
- CONICET, Instituto de Investigaciones Biológicas y Tecnológicas (IIByT), Córdoba, Argentina
| | - Nancy Salvatierra
- Facultad Ciencias Exactas, Físicas y Naturales, Departamento de Química, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, Córdoba, 5016, Argentina
- CONICET, Instituto de Investigaciones Biológicas y Tecnológicas (IIByT), Córdoba, Argentina
| | - Romina Comín
- Facultad Ciencias Exactas, Físicas y Naturales, Departamento de Química, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, Córdoba, 5016, Argentina
- CONICET, Instituto de Investigaciones Biológicas y Tecnológicas (IIByT), Córdoba, Argentina
| | - Tomas Tempesti
- Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, X5000HUA, Argentina
- INFIQC-CONICET, Instituto de Investigaciones en Físico-Química de Córdoba, Córdoba, Argentina
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Hong G, Chang JE. Enhancing Cancer Treatment Through Combined Approaches: Photodynamic Therapy in Concert with Other Modalities. Pharmaceutics 2024; 16:1420. [PMID: 39598543 PMCID: PMC11597730 DOI: 10.3390/pharmaceutics16111420] [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: 10/04/2024] [Revised: 10/27/2024] [Accepted: 11/05/2024] [Indexed: 11/29/2024] Open
Abstract
This review explores the role of photodynamic therapy (PDT) as an adjunctive treatment for cancers, with a focus on its potential to enhance the effects of established therapies like chemotherapy, surgery, and radiotherapy. Given the limitations of conventional cancer treatments, PDT's ability to improve therapeutic outcomes through combination strategies is examined. In cancers such as lung, breast, cholangiocarcinoma, and cervical, PDT shows promise in enhancing response rates, reducing recurrence, and minimizing adverse effects when used alongside standard modalities. This study highlights current findings on PDT's mechanisms in complementing chemotherapy, augmenting surgical precision, and enhancing radiotherapeutic effects, thus offering a multi-faceted approach to cancer treatment. Additionally, insights into the clinical application of PDT in these cancers emphasize its potential for reducing tumor resistance and supporting more effective, personalized care. By providing an overview of PDT's synergistic applications across diverse cancer types, this review underscores its emerging significance in oncology as a tool to address traditional treatment limitations. Ultimately, this review aims to inform and inspire researchers and clinicians seeking to refine and innovate cancer therapy strategies through PDT integration, contributing to the advancement of more effective, synergistic cancer treatments.
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Affiliation(s)
| | - Ji-Eun Chang
- College of Pharmacy, Dongduk Women’s University, Seoul 02748, Republic of Korea
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Anand S, Hasan T, Maytin EV. Treatment of nonmelanoma skin cancer with pro-differentiation agents and photodynamic therapy: Preclinical and clinical studies (Review). Photochem Photobiol 2024; 100:1541-1560. [PMID: 38310633 PMCID: PMC11297983 DOI: 10.1111/php.13914] [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: 11/07/2023] [Revised: 12/30/2023] [Accepted: 01/16/2024] [Indexed: 02/06/2024]
Abstract
Photodynamic therapy (PDT) is a nonscarring cancer treatment in which a pro-drug (5-aminolevulinic acid, ALA) is applied, converted into a photosensitizer (protoporphyrin IX, PpIX) which is then activated by visible light. ALA-PDT is now popular for treating nonmelanoma skin cancer (NMSC), but can be ineffective for larger skin tumors, mainly due to inadequate production of PpIX. Work over the past two decades has shown that differentiation-promoting agents, including methotrexate (MTX), 5-fluorouracil (5FU) and vitamin D (Vit D) can be combined with ALA-PDT as neoadjuvants to promote tumor-specific accumulation of PpIX, enhance tumor-selective cell death, and improve therapeutic outcome. In this review, we provide a historical perspective of how the combinations of differentiation-promoting agents with PDT (cPDT) evolved, including Initial discoveries, biochemical and molecular mechanisms, and clinical translation for the treatment of NMSCs. For added context, we also compare the differentiation-promoting neoadjuvants with some other clinical PDT combinations such as surgery, laser ablation, iron-chelating agents (CP94), and immunomodulators that do not induce differentiation. Although this review focuses mainly on the application of cPDT for NMSCs, the concepts and findings described here may be more broadly applicable towards improving the therapeutic outcomes of PDT treatment for other types of cancers.
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Affiliation(s)
- Sanjay Anand
- Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
- Dermatology and Plastic Surgery Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
- Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114
| | - Edward V Maytin
- Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
- Dermatology and Plastic Surgery Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
- Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114
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9
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Tang X, Li Y, Zhu T, Lv L, Liu J. Low-dose X-ray stimulated NO-releasing nanocomposites for closed-loop dual-mode cancer therapy. Biomater Sci 2024; 12:4211-4225. [PMID: 38980700 DOI: 10.1039/d4bm00593g] [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: 07/10/2024]
Abstract
X-ray-excited photodynamic therapy (X-PDT) employs X-rays as an energy source, overcoming the light penetration limitations of traditional photodynamic therapy (PDT) but is constrained by high-energy radiation and the hypoxic tumor microenvironment. Low-dose X-ray-excited photodynamic therapy and reduction of mitochondrial oxygen consumption can serve as significant breakthroughs in overcoming these barriers. In this study, NaLuF4:Tb/Gd (15%/5%)@NaYF4 (ScNP) nanoparticles adsorbing the photosensitizer MC540 and loaded with α-(nitrate ester) acid (NEAA) were prepared as low X-ray dose triggered nano-scintillators. The final product obtained was NaLuF4:Tb/Gd (15%/5%)@NaYF4@mSiO2@MC540@NEAA (ScNP-MS@MC540@NEAA) nanocomposites, which exhibited intense green luminescence. X-PDT generates cytotoxic reactive oxygen species (ROS) with minimal ionizing radiation damage. Simultaneously, NEAA reacts with glutathione (GSH) to generate nitric oxide (NO) for gaseous treatment of the damaged mitochondrial respiratory chain to reduce oxygen consumption and alleviate hypoxia, enhancing the X-PDT efficacy and realizing a closed-loop treatment. The superoxide ions (˙O2-) can rapidly react with NO produced to form the highly cytotoxic reactive nitrogen species (RNS) peroxynitrite anion (ONOO-), which exhibits higher cytotoxicity compared to ROS. Furthermore, GSH scavenges toxic ROS and maintains the physiological function of tumor cells. It can induce cancer cell overoxidation and nitrosative stress. This work describes a low-dose X-ray-triggered X-PDT system with total radiation of 50 mGy, which involves GSH consumption, self-supplied NO, mitochondrial damage alleviation, and hypoxia relief to generate ROS and RNS, forming a closed-loop anti-hypoxia dual-mode system with synergistically enhanced anti-tumor effects, without significant biological side effects. It provides a promising platform for deep-seated tumor X-PDT with considerable application prospects.
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Affiliation(s)
- Xiaoli Tang
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, PR China.
| | - Yong Li
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, PR China.
| | - Tao Zhu
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, PR China.
| | - Longhao Lv
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, PR China.
| | - Jinliang Liu
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, PR China.
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Hajfathalian M, Mossburg KJ, Radaic A, Woo KE, Jonnalagadda P, Kapila Y, Bollyky PL, Cormode DP. A review of recent advances in the use of complex metal nanostructures for biomedical applications from diagnosis to treatment. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1959. [PMID: 38711134 PMCID: PMC11114100 DOI: 10.1002/wnan.1959] [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: 01/14/2024] [Revised: 03/31/2024] [Accepted: 04/01/2024] [Indexed: 05/08/2024]
Abstract
Complex metal nanostructures represent an exceptional category of materials characterized by distinct morphologies and physicochemical properties. Nanostructures with shape anisotropies, such as nanorods, nanostars, nanocages, and nanoprisms, are particularly appealing due to their tunable surface plasmon resonances, controllable surface chemistries, and effective targeting capabilities. These complex nanostructures can absorb light in the near-infrared, enabling noteworthy applications in nanomedicine, molecular imaging, and biology. The engineering of targeting abilities through surface modifications involving ligands, antibodies, peptides, and other agents potentiates their effects. Recent years have witnessed the development of innovative structures with diverse compositions, expanding their applications in biomedicine. These applications encompass targeted imaging, surface-enhanced Raman spectroscopy, near-infrared II imaging, catalytic therapy, photothermal therapy, and cancer treatment. This review seeks to provide the nanomedicine community with a thorough and informative overview of the evolving landscape of complex metal nanoparticle research, with a specific emphasis on their roles in imaging, cancer therapy, infectious diseases, and biofilm treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Diagnostic Tools > Diagnostic Nanodevices.
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Affiliation(s)
- Maryam Hajfathalian
- Department of Biomedical Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102
- Division of Infectious Diseases, School of Medicine, Stanford University, Stanford, CA 94305
| | - Katherine J. Mossburg
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, 1 Silverstein, Philadelphia, Pennsylvania 19104, United States
| | - Allan Radaic
- School of Dentistry, University of California Los Angeles
| | - Katherine E. Woo
- Division of Infectious Diseases, School of Medicine, Stanford University, Stanford, CA 94305
| | - Pallavi Jonnalagadda
- Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Yvonne Kapila
- School of Dentistry, University of California Los Angeles
| | - Paul L. Bollyky
- Division of Infectious Diseases, Department of Medicine, Stanford University
| | - David P. Cormode
- Department of Radiology, Department of Bioengineering, University of Pennsylvania
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11
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Anand S, Shen A, Cheng CE, Chen J, Powers J, Rayman P, Diaz M, Hasan T, Maytin EV. Combination of vitamin D and photodynamic therapy enhances immune responses in murine models of squamous cell skin cancer. Photodiagnosis Photodyn Ther 2024; 45:103983. [PMID: 38281610 PMCID: PMC11197882 DOI: 10.1016/j.pdpdt.2024.103983] [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: 12/03/2023] [Revised: 01/10/2024] [Accepted: 01/17/2024] [Indexed: 01/30/2024]
Abstract
Improved treatment outcomes for non-melanoma skin cancers can be achieved if Vitamin D (Vit D) is used as a neoadjuvant prior to photodynamic therapy (PDT). However, the mechanisms for this effect are unclear. Vit D elevates protoporphyrin (PpIX) levels within tumor cells, but also exerts immune-modulatory effects. Here, two murine models, UVB-induced actinic keratoses (AK) and human squamous cell carcinoma (A431) xenografts, were used to analyze the time course of local and systemic immune responses after PDT ± Vit D. Fluorescence immunohistochemistry of tissues and flow analysis (FACS) of blood were employed. In tissue, damage-associated molecular patterns (DAMPs) were increased, and infiltration of neutrophils (Ly6G+), macrophages (F4/80+), and dendritic cells (CD11c+) were observed. In most cases, Vit D alone or PDT alone increased cell recruitment, but Vit D + PDT showed even greater recruitment effects. Similarly for T cells, increased infiltration of total (CD3+), cytotoxic (CD8+) and regulatory (FoxP3+) T-cells was observed after Vit D or PDT, but the increase was even greater with the combination. FACS analysis revealed a variety of interesting changes in circulating immune cell levels. In particular, neutrophils decreased in the blood after Vit D, consistent with migration of neutrophils into AK lesions. Levels of cells expressing the PD-1+ checkpoint receptor were reduced in AKs following Vit D, potentially counteracting PD-1+ elevations seen after PDT alone. In summary, Vit D and ALA-PDT, two treatments with individual immunogenic effects, may be advantageous in combination to improve treatment efficacy and management of AK in the dermatology clinic.
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Affiliation(s)
- Sanjay Anand
- Department of Biomedical Engineering, Cleveland Clinic, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Dermatology and Plastic Surgery Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
| | - Alan Shen
- Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Cheng-En Cheng
- Department of Biomedical Engineering, Cleveland Clinic, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Jacky Chen
- Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Jennifer Powers
- Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Pat Rayman
- Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Marcela Diaz
- Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114
| | - Edward V Maytin
- Department of Biomedical Engineering, Cleveland Clinic, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Dermatology and Plastic Surgery Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114.
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12
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Li J, Zhang Y, Zhang G, Zhang L, Zhou Z, Wang P, Wang X. Modified painless photodynamic therapy for facial multiple actinic keratosis in China: A prospective split-face control study. Lasers Surg Med 2023; 55:871-879. [PMID: 37814511 DOI: 10.1002/lsm.23728] [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: 05/29/2023] [Revised: 09/08/2023] [Accepted: 09/21/2023] [Indexed: 10/11/2023]
Abstract
BACKGROUND Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for multiple actinic keratosis (AK). However, PDT-induced pain often discontinues the therapy to reduce its efficacy, limiting its application. If modified painless PDT schedule with shorter photosensitizer dressing and higher dose illumination could achieve good efficacy in AK, it is still unknown. OBJECTIVES To explore the efficacy and pain tolerance of the modified painless PDT (M-PDT) in facial multiple AK. METHODS A split-face controlled clinical study including 14 patients with facial multiple AK was conducted. The patients received conventional PDT (C-PDT) on the left and M-PDT in the contralateral area. The left area (C-PDT) was illuminated by a red light-emitting diode light (144 J/cm2 ) after applying the 10% ALA cream for 3 h; the other had illumination for a total light dose of 288 J/cm2 after applying the 10% ALA cream for 0.5 h. The primary endpoint was the lesion clearance rate at 1-month postthree sessions of PDT. Secondary endpoints included pain scores, the incidence of adverse events during treatment, and cosmetic outcomes. RESULTS At 1 month following three treatments, the total lesion clearance rate was comparable between M-PDT and C-PDT (91.6% vs. 89.0%). While the lesion clearance rate of M-PDT was higher than that of C-PDT in the Grade III lesions (86.5% vs. 72.0%, respectively) (p < 0.05). M-PDT achieved a 100% lesion clearance rate for Grade I lesions earlier than C-PDT, with M-PDT treated twice and C-PDT treated thrice. Moreover, the pain score during illumination was significantly lower for M-PDT than for C-PDT (p < 0.01). Regarding photoaging, the Global Subjective Skin Aging Assessment score showed that the total and atrophy scores of C-PDT and M-PDT were significantly improved, and M-PDT also reduced discoloration. There was no significant difference in adverse reactions between C-PDT and M-PDT. CONCLUSIONS M-PDT is comparable to C-PDT's efficacy for treating facial multiple AK, resulting in much lower pain scores.
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Affiliation(s)
- Jiandan Li
- School of Medicine, Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China
| | - Yunfeng Zhang
- School of Medicine, Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China
| | - Guolong Zhang
- School of Medicine, Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China
| | - Linglin Zhang
- School of Medicine, Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China
| | - Zhongxia Zhou
- School of Medicine, Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China
| | - Peiru Wang
- School of Medicine, Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China
| | - Xiuli Wang
- School of Medicine, Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University, Shanghai, PR China
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13
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Moore A, Hurley K, Moore S, Moore L. Sustained resolution of nonmelanoma skin cancer with photodynamic therapy using 10% 5-aminolevulinic acid hydrochloride gel: A retrospective case series. JAAD Case Rep 2023; 38:148-151. [PMID: 37521188 PMCID: PMC10382802 DOI: 10.1016/j.jdcr.2023.06.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/01/2023] Open
Affiliation(s)
- Angela Moore
- Arlington Center for Dermatology, Arlington, Texas
- Arlington Research Center, Arlington, Texas
- Department of Dermatology, Baylor University Medical Center, Dallas, Texas
- Department of Medical Education, Texas Christian University School of Medicine, Fort Worth, Texas
- Department of Medical Education, Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, Texas
| | - Kara Hurley
- Department of Medical Education, Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, Texas
| | - Stephen Moore
- Arlington Center for Dermatology, Arlington, Texas
- Arlington Research Center, Arlington, Texas
| | - Luke Moore
- Arlington Center for Dermatology, Arlington, Texas
- Arlington Research Center, Arlington, Texas
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14
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Lima E, Reis LV. Photodynamic Therapy: From the Basics to the Current Progress of N-Heterocyclic-Bearing Dyes as Effective Photosensitizers. Molecules 2023; 28:5092. [PMID: 37446758 DOI: 10.3390/molecules28135092] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 06/16/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
Photodynamic therapy, an alternative that has gained weight and popularity compared to current conventional therapies in the treatment of cancer, is a minimally invasive therapeutic strategy that generally results from the simultaneous action of three factors: a molecule with high sensitivity to light, the photosensitizer, molecular oxygen in the triplet state, and light energy. There is much to be said about each of these three elements; however, the efficacy of the photosensitizer is the most determining factor for the success of this therapeutic modality. Porphyrins, chlorins, phthalocyanines, boron-dipyrromethenes, and cyanines are some of the N-heterocycle-bearing dyes' classes with high biological promise. In this review, a concise approach is taken to these and other families of potential photosensitizers and the molecular modifications that have recently appeared in the literature within the scope of their photodynamic application, as well as how these compounds and their formulations may eventually overcome the deficiencies of the molecules currently clinically used and revolutionize the therapies to eradicate or delay the growth of tumor cells.
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Affiliation(s)
- Eurico Lima
- CQ-VR-Chemistry Centre of Vila Real, University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801 Vila Real, Portugal
- CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilhã, Portugal
| | - Lucinda V Reis
- CQ-VR-Chemistry Centre of Vila Real, University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801 Vila Real, Portugal
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15
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Zhang J, Liu L, Li X, Shen X, Yang G, Deng Y, Hu Z, Zhang J, Lu Y. 5-ALA-PDT induced ferroptosis in keloid fibroblasts via ROS, accompanied by downregulation of xCT, GPX4. Photodiagnosis Photodyn Ther 2023:103612. [PMID: 37220842 DOI: 10.1016/j.pdpdt.2023.103612] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 04/25/2023] [Accepted: 05/09/2023] [Indexed: 05/25/2023]
Abstract
Keloids display many cancerous properties, including uncontrolled and invasive growth, high rates of recurrence as well as similar bioenergetics. 5-aminolevulinic acid-based photodynamic therapy (5-ALA-PDT) is an effective treatment that performs cytotoxic effects by producing reactive oxygen species (ROS), which is linked to lipid peroxidation and ferroptosis. Herein, we explored underlying mechanisms of 5-ALA-PDT against keloids. We identified that 5-ALA-PDT led to elevated levels of ROS and lipid peroxidation in keloid fibroblasts, accompanied by downregulation of xCT and GPX4, which are associated with anti-oxidation effects and ferroptosis inhibition. These results may indicate that 5-ALA-PDT treatment increases ROS while inhibiting xCT and GPX4, thus promoting lipid peroxidation to induce ferroptosis in keloid fibroblasts.
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Affiliation(s)
- Jiheng Zhang
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Lulu Liu
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Xinying Li
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Xiaoxiao Shen
- Bioengineering College of Chongqing University, Chongqing, China
| | - Guihong Yang
- Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, China
| | - Yumeng Deng
- Department of Dermatology, Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhengwei Hu
- Department of Urology, Daping Hospital, Army Medical University, Chongqing, China
| | - Junbo Zhang
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University, Chongqing, China.
| | - Yuangang Lu
- Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University, Chongqing, China.
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16
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Sahoo S, Pathak S, Kumar A, Nandi D, Chakravarty AR. Lysosome directed red light photodynamic therapy using glycosylated iron-(III) conjugates of boron-dipyrromethene. J Inorg Biochem 2023; 244:112226. [PMID: 37105008 DOI: 10.1016/j.jinorgbio.2023.112226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/10/2023] [Accepted: 04/12/2023] [Indexed: 04/29/2023]
Abstract
To overcome the drawbacks associated with chemotherapeutic and porphyrin-based photodynamic therapy (PDT) agents, the use of BODIPY (boron-dipyrromethene) scaffold has gained prominence in designing a new generation of photosensitizers-cum-cellular imaging agents. However, their poor cell permeability and limited solubility in aqueous medium inhibits the in-vitro application of their organic form. This necessitates the development of metal-BODIPY conjugates with improved physiological stability and enhanced therapeutic efficacy. We have designed two iron(III)-BODIPY conjugates, [Fe(L1/2)(L3)Cl] derived from benzyl-dipicolylamine and its glycosylated analogue along with a BODIPY-tagged catecholate. The complexes showed intense absorption bands (ε ∼ 55,000 M-1 cm-1) and demonstrated apoptotic PDT activity upon red-light irradiation (30 J/cm2, 600-720 nm). The complex with singlet oxygen quantum yield value of ∼0.34 gave sub-micromolar IC50 (half-maximal inhibitory concentration) value (∼0.08 μM) in both HeLa and H1299 cancer cells with a photocytotoxicity index value of >1200. Both the complexes were found to have significantly lower cytotoxic effects in non-cancerous HPL1D (human peripheral lung epithelial) cells. Singlet oxygen was determined to be the prime reactive oxygen species (ROS) responsible for cell damage from pUC19 DNA photo-cleavage studies, 1,3-diphenylisobenzofuran and SOSG (Singlet Oxygen Sensor Green) assays. Cellular imaging studies showed excellent fluorescence from complex 2 within 4 h, with localization in lysosomes. Significant drug accumulation into the core of 3D multicellular tumor spheroids was observed within 8 h from intense in-vitro emission. The complexes exemplify iron-based targeted PDT agents and show promising results as potential transition metal-based drugs for ROS mediated red light photocytotoxicity with low dosage requirement.
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Affiliation(s)
- Somarupa Sahoo
- Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560012, India
| | - Sanmoy Pathak
- Department of Biochemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560012, India
| | - Arun Kumar
- Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560012, India
| | - Dipankar Nandi
- Department of Biochemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560012, India.
| | - Akhil R Chakravarty
- Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560012, India.
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17
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Chen Y, Deng H, Yang L, Guo L, Feng M. Desferrioxamine Enhances 5-Aminolaevulinic Acid- Induced Protoporphyrin IX Accumulation and Therapeutic Efficacy for Hypertrophic Scar. J Pharm Sci 2023; 112:1635-1643. [PMID: 36682488 DOI: 10.1016/j.xphs.2023.01.015] [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: 07/05/2022] [Revised: 01/15/2023] [Accepted: 01/15/2023] [Indexed: 01/22/2023]
Abstract
Hypertrophic scar is a common problem after skin burns or trauma which brings physical, psychological, and cosmetic problems to patients. Photodynamic therapy with 5-aminolevulinic acid (5-ALA) is a promising therapy for hypertrophic scar. However, clinical applications of 5-ALA are limited because of the low permeability of 5-ALA in the skin stratum corneum and the rapid binding of protoporphyrin IX (PpIX) with iron ions, which lead to insufficient PpIX production in target tissues. Herein, a mixture of 5-ALA and DFO (deferoxamine, a special iron chelator) was applied for the treatment of hypertrophic scar. 5-ALA/DFO could efficiently block the biotransformation of PpIX to heme, thus realizing a significant accumulation of photosensitizer. In addition, injection locally into the lesion was applied, which combined with enhanced photodynamic therapy to destroy hypertrophic scar fibroblasts. In vitro experiments showed that 5-ALA/DFO could increase more ROS generation by increasing the accumulation of PpIX, resulting in the apoptosis of hypertrophic scar fibroblasts. Furthermore, 5-ALA/DFO inhibited the proliferation and migration of hypertrophic scar fibroblasts. In vivo study showed that 5-ALA/DFO could effectively inhibit the formation of proliferative scar. Therefore, 5-ALA/DFO has the potential to enhance the photodynamic therapy of 5-ALA and provides a new treatment strategy for hypertrophic scar.
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Affiliation(s)
- Yiman Chen
- School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou, 510006, PR China
| | - Huihui Deng
- School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou, 510006, PR China
| | - Liya Yang
- School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou, 510006, PR China
| | - Ling Guo
- School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou, 510006, PR China; School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, PR China.
| | - Min Feng
- School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou, 510006, PR China.
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18
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Multifunctional Photoactive Nanomaterials for Photodynamic Therapy against Tumor: Recent Advancements and Perspectives. Pharmaceutics 2022; 15:pharmaceutics15010109. [PMID: 36678738 PMCID: PMC9866498 DOI: 10.3390/pharmaceutics15010109] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/16/2022] [Accepted: 12/20/2022] [Indexed: 12/31/2022] Open
Abstract
Numerous treatments are available for cancer, including chemotherapy, immunotherapy, radiation therapy, hormone therapy, biomarker testing, surgery, photodynamic therapy, etc. Photodynamic therapy (PDT) is an effective, non-invasive, novel, and clinically approved strategy to treat cancer. In PDT, three main agents are utilized, i.e., photosensitizer (PS) drug, oxygen, and light. At first, the photosensitizer is injected into blood circulation or applied topically, where it quickly becomes absorbed or accumulated at the tumor site passively or actively. Afterward, the tumor is irradiated with light which leads to the activation of the photosensitizing molecule. PS produces the reactive oxygen species (ROS), resulting in the death of the tumor cell. However, the effectiveness of PDT for tumor destruction is mainly dependent on the cellular uptake and water solubility of photosensitizer molecules. Therefore, the delivery of photosensitizer molecules to the tumor cell is essential in PDT against cancer. The non-specific distribution of photosensitizer results in unwanted side effects and unsuccessful therapeutic outcomes. Therefore, to improve PDT clinical outcomes, the current research is mostly focused on developing actively targeted photosensitizer molecules, which provide a high cellular uptake and high absorption capacity to the tumor site by overcoming the problem associated with conventional PDT. Therefore, this review aims to provide current knowledge on various types of actively and passively targeted organic and inorganic nanocarriers for different cancers.
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19
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Bae I, Kim TG, Kim T, Kim D, Kim DH, Jo J, Lee YJ, Jeong YI. Phenethyl Isothiocyanate-Conjugated Chitosan Oligosaccharide Nanophotosensitizers for Photodynamic Treatment of Human Cancer Cells. Int J Mol Sci 2022; 23:13802. [PMID: 36430279 PMCID: PMC9693342 DOI: 10.3390/ijms232213802] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 11/02/2022] [Accepted: 11/07/2022] [Indexed: 11/11/2022] Open
Abstract
The aim of this study is to synthesize phenethyl-conjugated chitosan oligosaccharide (COS) (abbreviated as ChitoPEITC) conjugates and then fabricate chlorin E6 (Ce6)-incorporated nanophotosensitizers for photodynamic therapy (PDT) of HCT-116 colon carcinoma cells. PEITC was conjugated with the amine group of COS. Ce6-incorporated nanophotosensitizers using ChitoPEITC (ChitoPEITC nanophotosensitizers) were fabricated by dialysis method. 1H nuclear magnetic resonance (NMR) spectra showed that specific peaks of COS and PEITC were observed at ChitoPEITC conjugates. Transmission electron microscope (TEM) confirmed that ChitoPEITC nanophotosensitizers have spherical shapes with small hydrodynamic diameters less than 200 nm. The higher PEITC contents in the ChitoPEITC copolymer resulted in a slower release rate of Ce6 from nanophotosensitizers. Furthermore, the higher Ce6 contents resulted in a slower release rate of Ce6. In cell culture study, ChitoPEITC nanophotosensitizers showed low toxicity against normal CCD986Sk human skin fibroblast cells and HCT-116 human colon carcinoma cells in the absence of light irradiation. ChitoPEITC nanophotosensitizers showed a significantly higher Ce6 uptake ratio than that of free Ce6. Under light irradiation, cellular reactive oxygen species (ROS) production of nanophotosensitizers was significantly higher than that of free Ce6. Especially, PEITC and/or ChitoPEITC themselves contributed to the production of cellular ROS regardless of light irradiation. ChitoPEITC nanophotosensitizers showed significantly higher PDT efficacy against HCT-116 cells than that of free Ce6. These results indicate that ChitoPEITC nanophotosensitizers have superior potential in Ce6 uptake, ROS production and PDT efficacy. In the HCT-116 cell-bearing mice tumor-xenograft model, ChitoPEITC nanophotosensitizers efficiently inhibited growth of tumor volume rather than free Ce6. In the animal imaging study, ChitoPEITC nanophotosensitizers were concentrated in the tumor tissue, i.e., fluorescence intensity in the tumor tissue was stronger than that of other tissues. We suggest that ChitoPEITC nanophotosensitizers are a promising candidate for the treatment of human colon cancer cells.
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Affiliation(s)
- Inho Bae
- Department of Dental Materials, College of Dentistry, Chosun University, Gwangju 61452, Korea
| | - Taeyu Grace Kim
- Tyros Biotechnology Inc., 75 Kneeland St. 14 floors, Boston, MA 02111, USA
- Brookline High School, 115 Greenough St., Brookline, MA 02445, USA
| | - Taeyeon Kim
- College of Art & Science, University of Pennsylvania, 249 S 36th St., Philadelphia, PA 19104, USA
| | - Dohoon Kim
- Tyros Biotechnology Inc., 75 Kneeland St. 14 floors, Boston, MA 02111, USA
| | - Doug-Hoon Kim
- Department of Optometry, Masan University, Changwon 51217, Korea
| | - Jaewon Jo
- Gwangju Center, Korea Basic Science Institute, Gwangju 61186, Korea
| | - Young-Ju Lee
- Gwangju Center, Korea Basic Science Institute, Gwangju 61186, Korea
| | - Young-Il Jeong
- Tyros Biotechnology Inc., 75 Kneeland St. 14 floors, Boston, MA 02111, USA
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20
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Mazur A, Koziorowska K, Dynarowicz K, Aebisher D, Bartusik-Aebisher D. Vitamin D and Vitamin D3 Supplementation during Photodynamic Therapy: A Review. Nutrients 2022; 14:nu14183805. [PMID: 36145180 PMCID: PMC9502525 DOI: 10.3390/nu14183805] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/10/2022] [Accepted: 09/13/2022] [Indexed: 11/25/2022] Open
Abstract
Photodynamic therapy is an unconventional yet increasingly common method of treating dermatological diseases and cancer that is implemented more often in adults than in children. Current clinical uses include treatment of actinic keratosis, superficial basal cell carcinomas, and acne. Despite its high efficiency, photodynamic therapy support supplements have recently been reported in the literature, including calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D, and vitamin D3 cholecalciferol. In clinical trials, photodynamic therapy enhanced with vitamin D or D3 supplementation has been reported for treatment of squamous cell skin cancers, actinic keratosis, and psoriasis. Experimental research on the effect of photodynamic therapy with vitamin D or D3 has also been carried out in breast cancer cell lines and in animal models. The aim of this review is to evaluate the usefulness and effectiveness of vitamin D and D3 as supports for photodynamic therapy. For this purpose, the Pubmed and Scopus literature databases were searched. The search keyword was: “vitamin D in photodynamic therapy”. In the analyzed articles (1979–2022), the authors found experimental evidence of a positive effect of vitamin D and D3 when used in conjunction with photodynamic therapy. An average of 6–30% (in one case, up to 10 times) increased response to photodynamic therapy was reported in combination with vitamin D and D3 as compared to photodynamic therapy alone. Implementing vitamin D and D3 as a supplement to photodynamic therapy is promising and may lead to further clinical trials and new clinical methodologies.
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Affiliation(s)
- Anna Mazur
- Students Biochemistry Science Club URCell, Medical College of the University of Rzeszów, 35-959 Rzeszów, Poland
| | - Katarzyna Koziorowska
- Students English Division Science Club, 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
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College of the University of Rzeszów, 35-959 Rzeszów, Poland
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College of the University of Rzeszów, 35-959 Rzeszów, Poland
- Correspondence:
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21
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Anand S, Heusinkveld LE, Cheng CE, Lefatshe L, De Silva P, Hasan T, Maytin EV. Combination of 5-Fluorouracil with Photodynamic Therapy: Enhancement of Innate and Adaptive Immune Responses in a Murine Model of Actinic Keratosis. Photochem Photobiol 2022; 99:437-447. [PMID: 36039609 DOI: 10.1111/php.13706] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 08/19/2022] [Indexed: 11/29/2022]
Abstract
We previously showed that a combination of differentiation-inducing agents (5-fluorouracil, vitamin D3, or methotrexate) and aminolevulinate-based photodynamic therapy (PDT) improves clinical responses by enhancing protoporphyrin IX (PpIX) photosensitizer levels and cell death. Here, we show that in addition to its previously known effects, 5-fluorouracil (5FU) enhances PDT-induced tumor-regressing immunity. Murine actinic keratoses (AK) were treated with topical 5FU or vehicle for three days prior to ALA application, followed by blue light illumination (~417 nm). Lesions were harvested for time-course analyses of innate immune cell recruitment into lesions, i.e., neutrophils (Ly6G+) and macrophages (F4/80+), which peaked at 72 hours and 1 week post PDT, respectively, and was greater in 5FU treated lesions. Enhanced infiltration of activated T cells (CD3+) throughout the time course, and of cytotoxic T cells (CD8+) at 1 - 2 weeks post PDT, also occurred in 5FU treated lesions. 5FU pretreatment reduced the presence of cells expressing the immune checkpoint marker PD-1 at ~72 hours post PDT, favoring cytotoxic T cell activity. A combination of 5FU and PDT, each individually known to induce long-term tumor-targeting immune responses in addition to their more immediate effects on cancer cells, may synergize to provide better management of squamous precancers.
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Affiliation(s)
- Sanjay Anand
- Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.,Dermatology and Plastic Surgery Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.,Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Lauren E Heusinkveld
- Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Cheng-En Cheng
- Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Lefatshe Lefatshe
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Pushpamali De Silva
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Edward V Maytin
- Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.,Dermatology and Plastic Surgery Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.,Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.,Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA
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22
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Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial. J Am Acad Dermatol 2022; 87:80-86. [PMID: 35314199 PMCID: PMC9233022 DOI: 10.1016/j.jaad.2022.02.067] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/23/2022] [Accepted: 02/24/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND In mouse models of skin cancer, high-dose oral vitamin D3 (VD3; cholecalciferol) combined with photodynamic therapy (PDT) can improve the clearance of squamous precancers (actinic keratoses [AKs]). OBJECTIVE To determine whether oral VD3 can improve the clinical efficacy of a painless PDT regimen in humans with AK. METHODS The baseline lesion counts and serum 25-hydroxyvitamin D3 levels were determined. In group 1, 29 patients underwent gentle debridement and 15-minute aminolevulinic acid preincubation with blue light (30 minutes; 20 J/cm2). In group 2, 29 patients took oral VD3 (10,000 IU daily for 5 or 14 days) prior to debridement and PDT. Lesion clearance was assessed at 3 to 6 months. RESULTS In group 1, the mean clearance rates of facial AK were lower in patients with VD3 deficiency (25-hydroxyvitamin D3 level < 31 ng/dL; clearance rate, 40.9% ± 42%) than in patients with normal 25-hydroxyvitamin D3 levels (62.6% ± 14.2%). High-dose VD3 supplementation (group 2) significantly improved the overall AK lesion response (72.5% ± 13.6%) compared with that in group 1 (54.4% ± 22.8%). No differences in side effects were noted. LIMITATIONS Nonrandomized trial design (interventional cohort matched to registry-based controls). CONCLUSIONS Oral VD3 pretreatment significantly improves AK clinical responses to PDT. The regimen appears promising and well tolerated.
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23
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Zeng Q, Zhou C, Zhang Y, Yan G, Wang X. Modified 5-aminolevulinic acid photodynamic therapy reduces pain and improves therapeutic effects in cutaneous squamous cell carcinoma mouse model. Lasers Surg Med 2022; 54:804-812. [PMID: 35066886 DOI: 10.1002/lsm.23516] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/29/2021] [Accepted: 01/03/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Conventional ALA-PDT (C-PDT) has limited efficacy in cutaneous squamous cell carcinoma (cSCC), and there is obvious pain during treatment, which limits its clinical application. We sought to modify photodynamic therapy into a more painless and effective treatment. METHODS We modified C-PDT by reducing the incubation time of the pro-sensitizer and increasing the light dose; we named this method modified ALA-PDT (M-PDT). We compared the pain response and curative effect between C-PDT and M-PDT in cSCC mouse models. Pain-related proteins were examined by western blot analysis and immunohistochemistry. Tumor progression-associated signaling pathways were analyzed by RNA-seq and western blot analysis. Reactive oxygen species (ROS) generation was measured with a ROS test kit and Microplate reader. RESULTS M-PDT greatly reduced pain during treatment. Interestingly, when the cSCC tumor volume increased to 150-200 mm3 , M-PDT almost completely eliminated the tumors, while C-PDT did not. The better curative effect of M-PDT might be due to the stronger suppression of the Stat3, Erk1/2, and mTOR signaling pathways. Moreover, flow cytometry demonstrated that M-PDT could recruit CD8+ T cells to inhibit cSCC progression. Further investigation determined that the different mechanisms of C-PDT and M-PDT were related to more ROS generation induced by M-PDT. CONCLUSIONS Our results suggest that M-PDT, which is more painless and effective than C-PDT, is expected to provide a solution for the treatment of cSCC.
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Affiliation(s)
- Qingyu Zeng
- Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Chu Zhou
- Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yunfeng Zhang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Guorong Yan
- Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xiuli Wang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China
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24
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Li C, Wang Y, Wu S, Zhuang W, Huang Z, Zhou L, Li Y, Chen M, You J. Direct [4 + 2] Cycloaddition to Isoquinoline-Fused Porphyrins for Near-Infrared Photodynamic Anticancer Agents. Org Lett 2022; 24:175-180. [PMID: 34889619 DOI: 10.1021/acs.orglett.1c03804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The synthesis of efficient porphyrin-based photosensitizers with intense near-infrared (NIR) absorption is in high demand for photodynamic therapy (PDT) but remains a challenging task. Herein we show the construction of a type of isoquinoline-fused porphyrins 3 and 4 with an impressive NIR-absorbing capacity. In light of the extraordinary singlet oxygen generation capabilities of 3 upon NIR irradiation, the representative nanoparticles (3a-NPs) assembled show excellent tumoricidal behavior with good biocompatibility in the phototherapeutic window (650-850 nm).
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Affiliation(s)
- Chengming Li
- Laboratory of Heart Valve Disease, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, P. R. China
| | - Yinchan Wang
- Core Facility of West China Hospital, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, P. R. China
| | - Sisi Wu
- Core Facility of West China Hospital, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, P. R. China
| | - Weihua Zhuang
- Laboratory of Heart Valve Disease, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, P. R. China
| | - Zhenmei Huang
- Key Laboratory of Green Chemistry and Technology of the Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China
| | - Linsen Zhou
- Institute of Materials, Chinese Academy of Engineering Physics, Jiangyou 621908, P. R. China
| | - Yinggang Li
- Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, P. R. China
| | - Mao Chen
- Laboratory of Heart Valve Disease, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, P. R. China
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, P. R. China
| | - Jingsong You
- Key Laboratory of Green Chemistry and Technology of the Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China
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25
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Mansi M, Howley R, Chen B. Methods to Measure the Inhibition of ABCG2 Transporter and Ferrochelatase Activity to Enhance Aminolevulinic Acid-Protoporphyrin IX Fluorescence-Guided Tumor Detection and Resection. Methods Mol Biol 2022; 2394:823-835. [PMID: 35094360 DOI: 10.1007/978-1-0716-1811-0_43] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Aminolevulinic acid (ALA) has been clinically used as an intraoperative fluorescence probe for protoporphyrin IX (PpIX) fluorescence-guided tumor resection and a PDT agent for cancer treatment. Although tumor tissues often show increased ALA-PpIX fluorescence compared with normal tissues, which enables the use of ALA for tumor imaging and targeting, weak tumor PpIX fluorescence as well as the heterogeneity in tumor fluorescence severely limits its clinical application. Intracellular PpIX in tumor cells is reduced by two major mechanisms, efflux by ATP-binding cassette (ABC) transporters such as ABCG2 and bioconversion to form heme by ferrochelatase (FECH) in the heme biosynthesis pathway. Targeting these two predominant PpIX-reducing mechanisms for the enhancement of ALA-PpIX have yielded a plethora of promising results and stimulated the clinical exploration of these enhancement strategies. Here we describe our methods of evaluating chemicals for the inhibition of ABCG2 transporter and FECH activity. Our goal is to further encourage research and development of novel ABCG2 and FECH inhibitors and promote a rational use of these inhibitors to optimize ALA-based tumor detection and treatment.
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Affiliation(s)
- Matthew Mansi
- Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA
| | - Richard Howley
- Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA
| | - Bin Chen
- Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA. .,Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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26
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An Optimized Approach for Prostate Image Segmentation Using K-Means Clustering Algorithm with Elbow Method. COMPUTATIONAL INTELLIGENCE AND NEUROSCIENCE 2021; 2021:4553832. [PMID: 34819951 PMCID: PMC8608531 DOI: 10.1155/2021/4553832] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 10/26/2021] [Indexed: 01/05/2023]
Abstract
Prostate cancer disease is one of the common types that cause men's prostate damage all over the world. Prostate-specific membrane antigen (PSMA) expressed by type-II is an extremely attractive style for imaging-based diagnosis of prostate cancer. Clinically, photodynamic therapy (PDT) is used as noninvasive therapy in treatment of several cancers and some other diseases. This paper aims to segment or cluster and analyze pixels of histological and near-infrared (NIR) prostate cancer images acquired by PSMA-targeting PDT low weight molecular agents. Such agents can provide image guidance to resection of the prostate tumors and permit for the subsequent PDT in order to remove remaining or noneradicable cancer cells. The color prostate image segmentation is accomplished using an optimized image segmentation approach. The optimized approach combines the k-means clustering algorithm with elbow method that can give better clustering of pixels through automatically determining the best number of clusters. Clusters' statistics and ratio results of pixels in the segmented images show the applicability of the proposed approach for giving the optimum number of clusters for prostate cancer analysis and diagnosis.
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27
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Algorri JF, Ochoa M, Roldán-Varona P, Rodríguez-Cobo L, López-Higuera JM. Photodynamic Therapy: A Compendium of Latest Reviews. Cancers (Basel) 2021; 13:4447. [PMID: 34503255 PMCID: PMC8430498 DOI: 10.3390/cancers13174447] [Citation(s) in RCA: 131] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/15/2022] Open
Abstract
Photodynamic therapy (PDT) is a promising therapy against cancer. Even though it has been investigated for more than 100 years, scientific publications have grown exponentially in the last two decades. For this reason, we present a brief compendium of reviews of the last two decades classified under different topics, namely, overviews, reviews about specific cancers, and meta-analyses of photosensitisers, PDT mechanisms, dosimetry, and light sources. The key issues and main conclusions are summarized, including ways and means to improve therapy and outcomes. Due to the broad scope of this work and it being the first time that a compendium of the latest reviews has been performed for PDT, it may be of interest to a wide audience.
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Affiliation(s)
- José Francisco Algorri
- Photonics Engineering Group, University of Cantabria, 39005 Santander, Spain; (M.O.); (P.R.-V.); (J.M.L.-H.)
- CIBER-bbn, Institute of Health Carlos III, 28029 Madrid, Spain;
- Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain
| | - Mario Ochoa
- Photonics Engineering Group, University of Cantabria, 39005 Santander, Spain; (M.O.); (P.R.-V.); (J.M.L.-H.)
- CIBER-bbn, Institute of Health Carlos III, 28029 Madrid, Spain;
- Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain
| | - Pablo Roldán-Varona
- Photonics Engineering Group, University of Cantabria, 39005 Santander, Spain; (M.O.); (P.R.-V.); (J.M.L.-H.)
- CIBER-bbn, Institute of Health Carlos III, 28029 Madrid, Spain;
- Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain
| | | | - José Miguel López-Higuera
- Photonics Engineering Group, University of Cantabria, 39005 Santander, Spain; (M.O.); (P.R.-V.); (J.M.L.-H.)
- CIBER-bbn, Institute of Health Carlos III, 28029 Madrid, Spain;
- Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain
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28
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Bienia A, Wiecheć-Cudak O, Murzyn AA, Krzykawska-Serda M. Photodynamic Therapy and Hyperthermia in Combination Treatment-Neglected Forces in the Fight against Cancer. Pharmaceutics 2021; 13:1147. [PMID: 34452108 PMCID: PMC8399393 DOI: 10.3390/pharmaceutics13081147] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 06/26/2021] [Accepted: 07/16/2021] [Indexed: 12/24/2022] Open
Abstract
Cancer is one of the leading causes of death in humans. Despite the progress in cancer treatment, and an increase in the effectiveness of diagnostic methods, cancer is still highly lethal and very difficult to treat in many cases. Combination therapy, in the context of cancer treatment, seems to be a promising option that may allow minimizing treatment side effects and may have a significant impact on the cure. It may also increase the effectiveness of anti-cancer therapies. Moreover, combination treatment can significantly increase delivery of drugs to cancerous tissues. Photodynamic therapy and hyperthermia seem to be ideal examples that prove the effectiveness of combination therapy. These two kinds of therapy can kill cancer cells through different mechanisms and activate various signaling pathways. Both PDT and hyperthermia play significant roles in the perfusion of a tumor and the network of blood vessels wrapped around it. The main goal of combination therapy is to combine separate mechanisms of action that will make cancer cells more sensitive to a given therapeutic agent. Such an approach in treatment may contribute toward increasing its effectiveness, optimizing the cancer treatment process in the future.
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Affiliation(s)
| | | | | | - Martyna Krzykawska-Serda
- Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland; (A.B.); (O.W.-C.); (A.A.M.)
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29
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Wang X, Luo D, Basilion JP. Photodynamic Therapy: Targeting Cancer Biomarkers for the Treatment of Cancers. Cancers (Basel) 2021; 13:cancers13122992. [PMID: 34203805 PMCID: PMC8232794 DOI: 10.3390/cancers13122992] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 06/07/2021] [Accepted: 06/14/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Photodynamic therapy (PDT) is a minimally invasive treatment option that can kill cancerous cells by subjecting them to light irradiation at a specific wavelength. The main problem related to most photosensitizers is the lack of tumor selectivity, which leads to undesired uptake in normal tissues resulting in side effects. Passive targeting and active targeting are the two strategies to improve uptake in tumor tissues. This review focused on active targeting and summarizes recent active targeting approaches in which highly potent photosensitizers are rendered tumor-specific by means of an appended targeting moiety that interacts with a protein unique to, or at least significantly more abundant on, tumor cell surfaces compared to normal cells. Abstract Photodynamic therapy (PDT) is a well-documented therapy that has emerged as an effective treatment modality of cancers. PDT utilizes harmless light to activate non- or minimally toxic photosensitizers to generate cytotoxic species for malignant cell eradication. Compared with conventional chemotherapy and radiotherapy, PDT is appealing by virtue of the minimal invasiveness, its safety, as well as its selectivity, and the fact that it can induce an immune response. Although local illumination of the cancer lesions renders intrinsic selectivity of PDT, most photosensitizers used in PDT do not display significant tumor tissue selectivity. There is a need for targeted delivery of photosensitizers. The molecular identification of cancer antigens has opened new possibilities for the development of effective targeted therapy for cancer patients. This review provides a brief overview of recent achievements of targeted delivery of photosensitizers to cancer cells by targeting well-established cancer biomarkers. Overall, targeted PDT offers enhanced intracellular accumulation of the photosensitizer, leading to improved PDT efficacy and reduced toxicity to normal tissues.
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Affiliation(s)
- Xinning Wang
- Department of Biomedical Engineering, Case Western Reserve University, 11100 Euclid Ave, Wearn Building B-49, Cleveland, OH 44106, USA
- Correspondence: (X.W.); (J.P.B.); Tel.: +216-844-4848 (X.W.); +216-983-3246 (J.P.B.); Fax: +216-844-4987 (X.W. & J.P.B.)
| | - Dong Luo
- Department of Radiology, Case Western Reserve University, 11100 Euclid Ave, Wearn Building B-44, Cleveland, OH 44106, USA;
| | - James P. Basilion
- Department of Biomedical Engineering, Case Western Reserve University, 11100 Euclid Ave, Wearn Building B-49, Cleveland, OH 44106, USA
- Department of Radiology, Case Western Reserve University, 11100 Euclid Ave, Wearn Building B-44, Cleveland, OH 44106, USA;
- Correspondence: (X.W.); (J.P.B.); Tel.: +216-844-4848 (X.W.); +216-983-3246 (J.P.B.); Fax: +216-844-4987 (X.W. & J.P.B.)
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30
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Zhao M, Leggett E, Bourke S, Poursanidou S, Carter-Searjeant S, Po S, Palma do Carmo M, Dailey LA, Manning P, Ryan SG, Urbano L, Green MA, Rakovich A. Theranostic Near-Infrared-Active Conjugated Polymer Nanoparticles. ACS NANO 2021; 15:8790-8802. [PMID: 33978405 DOI: 10.1021/acsnano.1c01257] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Conjugated polymer nanoparticles (CPNs) based on a common solar cell material (PTB7) have been prepared, and their potential in theranostic applications based on bioimaging and photosensitizing capabilities has been evaluated. The main absorption and emission bands of the prepared CPNs both fell within the NIR-I (650-950 nm) transparency window, allowing facile and efficient implementation of our CPNs as bioimaging agents, as demonstrated in this work for A549 human lung cancer cell cultures. The prepared CPN samples were also shown to produce reactive oxygen species (ROS) upon photoexcitation in the near-infrared or ultraviolet spectral regions, both in aqueous solutions and in HaCaT keratinocyte cell cultures. Importantly, we show that the photosensitizing ability of our CPNs was largely determined by the nature of the stabilizing shell: coating the CPNs with a Pluronic F-127 copolymer led to an improvement of photoinitiated ROS production, while using poly[styrene-co-maleic anhydride] instead completely quenched said process. This work therefore demonstrates that the photosensitizing capability of CPNs can be modulated via an appropriate selection of stabilizing material and highlights the significance of this parameter for the on-demand design of theranostic probes based on CPNs.
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Affiliation(s)
- Miao Zhao
- Physics Department, King's College London, Strand Building, London, WC2R 2LS, U.K
| | - Edward Leggett
- Physics Department, King's College London, Strand Building, London, WC2R 2LS, U.K
| | - Struan Bourke
- Physics Department, King's College London, Strand Building, London, WC2R 2LS, U.K
| | - Souzana Poursanidou
- Department of Clinical, Pharmaceutical and Biological Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, U.K
| | | | - Steve Po
- Physics Department, King's College London, Strand Building, London, WC2R 2LS, U.K
| | | | - Lea Ann Dailey
- Department of Pharmaceutical Technology and Biopharmacy, University of Vienna, Vienna, 1090, Austria
| | - Philip Manning
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, Tyne and Wear NE2 4HH, U.K
| | - Sean G Ryan
- Department of Physics, Astronomy and Mathematics, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, U.K
- Centre for Advanced Biomedical Imaging, University College London, Gower Street, London, WC1E 6BT, U.K
| | - Laura Urbano
- Department of Clinical, Pharmaceutical and Biological Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, U.K
| | - Mark A Green
- Physics Department, King's College London, Strand Building, London, WC2R 2LS, U.K
| | - Aliaksandra Rakovich
- Physics Department, King's College London, Strand Building, London, WC2R 2LS, U.K
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31
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Current Prospects for Treatment of Solid Tumors via Photodynamic, Photothermal, or Ionizing Radiation Therapies Combined with Immune Checkpoint Inhibition (A Review). Pharmaceuticals (Basel) 2021; 14:ph14050447. [PMID: 34068491 PMCID: PMC8151935 DOI: 10.3390/ph14050447] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 04/29/2021] [Accepted: 05/03/2021] [Indexed: 12/21/2022] Open
Abstract
Photodynamic therapy (PDT) causes selective damage to tumor cells and vasculature and also triggers an anti-tumor immune response. The latter fact has prompted the exploration of PDT as an immune-stimulatory adjuvant. PDT is not the only cancer treatment that relies on electromagnetic energy to destroy cancer tissue. Ionizing radiation therapy (RT) and photothermal therapy (PTT) are two other treatment modalities that employ photons (with wavelengths either shorter or longer than PDT, respectively) and also cause tissue damage and immunomodulation. Research on the three modalities has occurred in different “silos”, with minimal interaction between the three topics. This is happening at a time when immune checkpoint inhibition (ICI), another focus of intense research and clinical development, has opened exciting possibilities for combining PDT, PTT, or RT with ICI to achieve improved therapeutic benefits. In this review, we surveyed the literature for studies that describe changes in anti-tumor immunity following the administration of PDT, PTT, and RT, including efforts to combine each modality with ICI. This information, collected all in one place, may make it easier to recognize similarities and differences and help to identify new mechanistic hypotheses toward the goal of achieving optimized combinations and tumor cures.
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32
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Anand S, Govande M, Yasinchak A, Heusinkveld L, Shakya S, Fairchild R, Maytin EV. Painless Photodynamic Therapy Triggers Innate and Adaptive Immune Responses in a Murine Model of UV-induced Squamous Skin Pre-cancer. Photochem Photobiol 2021; 97:607-617. [PMID: 33113217 PMCID: PMC10481390 DOI: 10.1111/php.13350] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 10/23/2020] [Indexed: 12/18/2022]
Abstract
Painless photodynamic therapy (p-PDT), which involves application of photosensitizer and immediate exposure to light to treat actinic keratosis (AK) in patients, causes negligible pain on the day of treatment but leads to delayed inflammation and effective lesion clearance (Kaw et al., J Am Acad Dermatol 2020). To better understand how p-PDT works, hairless mice with UV-induced AK were treated with p-PDT and monitored for 2 weeks. Lesion clearance after p-PDT was similar to clearance after conventional PDT (c-PDT). However, lesion biopsies showed minimal cell death and less production of reactive oxygen species (ROS) in p-PDT treated than in c-PDT-treated lesions. Interestingly, p-PDT triggered vigorous recruitment of immune cells associated with innate immunity. Neutrophils (Ly6G+) and macrophages (F4/80+) appeared at 4 h and peaked at 24 h after p-PDT. Damage-associated molecular patterns (DAMPs), including calreticulin, HMGB1, and HSP70, were expressed at maximum levels around 24 h post-p-PDT. Total T cells (CD3+) were increased at 24 h, whereas large increases in cytotoxic (CD8+) and regulatory (Foxp3+) T cells were observed at 1 and 2 weeks post-p-PDT. In summary, the ability of p-PDT to eliminate AK lesions, despite very little overt cellular damage, appears to involve stimulation of a local immune response.
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Affiliation(s)
- Sanjay Anand
- Department of Biomedical Engineering
- Dermatology and Plastic Surgery Institute
- Cleveland Clinic Lerner College of Medicine of CWRU, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | | | | | - Lauren Heusinkveld
- Cleveland Clinic Lerner College of Medicine of CWRU, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | | | - Robert Fairchild
- Department of Inflammation and Immunity, Lerner Research Institute
- Cleveland Clinic Lerner College of Medicine of CWRU, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Edward V. Maytin
- Department of Biomedical Engineering
- Dermatology and Plastic Surgery Institute
- Cleveland Clinic Lerner College of Medicine of CWRU, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
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33
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Pereira NAM, Laranjo M, Nascimento BFO, Simões JCS, Pina J, Costa BDP, Brites G, Braz J, Seixas de Melo JS, Pineiro M, Botelho MF, Pinho E Melo TMVD. Novel fluorinated ring-fused chlorins as promising PDT agents against melanoma and esophagus cancer. RSC Med Chem 2021; 12:615-627. [PMID: 34046633 PMCID: PMC8128062 DOI: 10.1039/d0md00433b] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 03/22/2021] [Indexed: 12/24/2022] Open
Abstract
Investigation of novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins, derived from 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, as PDT agents against melanoma and esophagus cancer is disclosed. Diol and diester fluorinated ring-fused chlorins, including derivatives with 2-(2-hydroxyethoxy)ethanamino groups at the phenyl rings, were obtained via a two-step methodology, combining SNAr and [8π + 2π] cycloaddition reactions. The short-chain PEG groups at the para-position of the phenyl rings together with the diol moiety at the fused pyrazole ring promote a red-shift of the Soret band, a decrease of the fluorescence quantum yield and an increase of the singlet oxygen formation quantum yield, improving the photophysical characteristics required to act as a photosensitizer. Introduction of these hydrophilic groups also improves the incorporation of the sensitizers by the cells reaching cellular uptake values of nearly 50% of the initial dose. The rational design led to a photosensitizer with impressive IC50 values, 13 and 27 nM against human melanoma and esophageal carcinoma cell lines, respectively.
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Affiliation(s)
- Nelson A M Pereira
- Coimbra Chemistry Centre (CQC) and Department of Chemistry, University of Coimbra 3004-535 Coimbra Portugal
| | - Mafalda Laranjo
- Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra 3000-548 Coimbra Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra 3000-548 Coimbra Portugal
- Clinical and Academic Centre of Coimbra 3000-548 Coimbra Portugal
| | - Bruno F O Nascimento
- Coimbra Chemistry Centre (CQC) and Department of Chemistry, University of Coimbra 3004-535 Coimbra Portugal
| | - João C S Simões
- Coimbra Chemistry Centre (CQC) and Department of Chemistry, University of Coimbra 3004-535 Coimbra Portugal
- Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra 3000-548 Coimbra Portugal
| | - João Pina
- Coimbra Chemistry Centre (CQC) and Department of Chemistry, University of Coimbra 3004-535 Coimbra Portugal
| | - Bruna D P Costa
- Coimbra Chemistry Centre (CQC) and Department of Chemistry, University of Coimbra 3004-535 Coimbra Portugal
- Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra 3000-548 Coimbra Portugal
| | - Gonçalo Brites
- Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra 3000-548 Coimbra Portugal
| | - João Braz
- Coimbra Chemistry Centre (CQC) and Department of Chemistry, University of Coimbra 3004-535 Coimbra Portugal
- Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra 3000-548 Coimbra Portugal
| | - J Sérgio Seixas de Melo
- Coimbra Chemistry Centre (CQC) and Department of Chemistry, University of Coimbra 3004-535 Coimbra Portugal
| | - Marta Pineiro
- Coimbra Chemistry Centre (CQC) and Department of Chemistry, University of Coimbra 3004-535 Coimbra Portugal
| | - Maria Filomena Botelho
- Institute of Biophysics and Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra 3000-548 Coimbra Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra 3000-548 Coimbra Portugal
- Clinical and Academic Centre of Coimbra 3000-548 Coimbra Portugal
| | - Teresa M V D Pinho E Melo
- Coimbra Chemistry Centre (CQC) and Department of Chemistry, University of Coimbra 3004-535 Coimbra Portugal
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Cheng Y, Zheng R, Wu X, Xu K, Song P, Wang Y, Yan J, Chen R, Li X, Zhang H. Thylakoid Membranes with Unique Photosystems Used to Simultaneously Produce Self-Supplying Oxygen and Singlet Oxygen for Hypoxic Tumor Therapy. Adv Healthc Mater 2021; 10:e2001666. [PMID: 33448152 DOI: 10.1002/adhm.202001666] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 12/13/2020] [Indexed: 12/24/2022]
Abstract
Photodynamic therapy (PDT) efficacy has been dramatically limited by the insufficient oxygen (O2 ) level in hypoxic tumors. Although various PDT nanosystems have been designed to deliver or produce O2 in support of reactive oxygen species (ROS) formation, the feature of asynchronous O2 generation and ROS formation still results in the low PDT efficacy. Herein, thylakoid membranes (TM) of chloroplasts is decorated on upconversion nanoparticles (UCNPs) to form UCTM NPs, aiming at realizing spatiotemporally synchronous O2 self-supply and ROS production. Upon 980 nm laser irradiation, UC NPs can emit the red light to activate both photosystem-I and photosystem-II of TM, the Z-scheme electronic structure of which facilitates water to produce O2 and further to singlet oxygen (1 O2 ). UCTM NPs showed excellent biocompatibility, and can effectively remove the hypoxic tumor of mice upon 980 nm laser irradiation. This study develops a new PDT strategy for hypoxic tumor therapy based on photosynthesis.
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Affiliation(s)
- Yan Cheng
- Laboratory of Chemical Biology Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China
- University of Science and Technology of China Hefei Anhui 230026 China
| | - Runxiao Zheng
- Laboratory of Chemical Biology Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China
- University of Science and Technology of China Hefei Anhui 230026 China
| | - Xiaqing Wu
- Laboratory of Chemical Biology Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China
- University of Science and Technology of China Hefei Anhui 230026 China
| | - Keqiang Xu
- Laboratory of Chemical Biology Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China
- University of Science and Technology of China Hefei Anhui 230026 China
| | - Panpan Song
- Laboratory of Chemical Biology Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China
- University of Science and Technology of China Hefei Anhui 230026 China
| | - Yanjing Wang
- Laboratory of Chemical Biology Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China
- University of Science and Technology of China Hefei Anhui 230026 China
| | - Jiao Yan
- Laboratory of Chemical Biology Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China
- University of Science and Technology of China Hefei Anhui 230026 China
| | - Rui Chen
- College of Science Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement Changchun University Changchun Jilin 130022 China
| | - Xi Li
- School of Chemistry and Life Science Changchun University of Technology Changchun Jilin 130012 China
| | - Haiyuan Zhang
- Laboratory of Chemical Biology Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China
- University of Science and Technology of China Hefei Anhui 230026 China
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Elzi DJ, Bauta WE, Sanchez JR, Das T, Mogare S, Zannes Fatland P, Iza M, Pertsemlidis A, Rebel VI. Identification of a novel mechanism for meso-tetra (4-carboxyphenyl) porphyrin (TCPP) uptake in cancer cells. FASEB J 2021; 35:e21427. [PMID: 33629776 DOI: 10.1096/fj.202000197r] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 01/13/2021] [Accepted: 01/22/2021] [Indexed: 01/23/2023]
Abstract
Porphyrins are used for cancer diagnostic and therapeutic applications, but the mechanism of how porphyrins accumulate in cancer cells remains elusive. Knowledge of how porphyrins enter cancer cells can aid the development of more accurate cancer diagnostics and therapeutics. To gain insight into porphyrin uptake mechanisms in cancer cells, we developed a flow cytometry assay to quantify cellular uptake of meso-tetra (4-carboxyphenyl) porphyrin (TCPP), a porphyrin that is currently being developed for cancer diagnostics. We found that TCPP enters cancer cells through clathrin-mediated endocytosis. The LDL receptor, previously implicated in the cellular uptake of other porphyrins, only contributes modestly to uptake. We report that TCPP instead binds strongly ( K D = 42 nM ) to CD320, the cellular receptor for cobalamin/transcobalamin II (Cbl/TCN2). Additionally, TCPP competes with Cbl/TCN2 for CD320 binding, suggesting that CD320 is a novel receptor for TCPP. Knockdown of CD320 inhibits TCPP uptake by up to 40% in multiple cancer cell lines, including lung, breast, and prostate cell lines, which supports our hypothesis that CD320 both binds to and transports TCPP into cancer cells. Our findings provide some novel insights into why porphyrins concentrate in cancer cells. Additionally, our study describes a novel function for the CD320 receptor which has been reported to transport only Cbl/TCN2 complexes.
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Affiliation(s)
- David J Elzi
- BioAffinity Technologies, Inc., San Antonio, TX, USA
| | | | | | - Trisha Das
- BioAffinity Technologies, Inc., San Antonio, TX, USA
| | - Shweta Mogare
- BioAffinity Technologies, Inc., San Antonio, TX, USA
| | | | - Moises Iza
- BioAffinity Technologies, Inc., San Antonio, TX, USA
| | - Alexander Pertsemlidis
- Department of Pediatrics, The University of Texas Health Science Center, San Antonio, TX, USA.,Department of Cell Systems & Anatomy, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.,Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.,Mays Cancer Center, UT Health San Antonio MD Anderson, San Antonio, TX, USA
| | - Vivienne I Rebel
- BioAffinity Technologies, Inc., San Antonio, TX, USA.,Department of Cell Systems & Anatomy, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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Rytlewski JD, Scalora N, Garcia K, Tanas M, Toor F, Miller B, Allen B, Milhem M, Monga V. Photodynamic Therapy Using Hippo Pathway Inhibitor Verteporfin: A Potential Dual Mechanistic Approach in Treatment of Soft Tissue Sarcomas. Cancers (Basel) 2021; 13:cancers13040675. [PMID: 33567506 PMCID: PMC7915813 DOI: 10.3390/cancers13040675] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 02/02/2021] [Accepted: 02/05/2021] [Indexed: 12/30/2022] Open
Abstract
Simple Summary Advanced sarcomas have yet to undergo improved outcomes seen in other cancer subtypes. Verteporfin has the potential to show landmark change in sarcoma due to its anti-proliferative properties: inhibition of the Hippo pathway and as photodynamic therapy. The effect of verteporfin on the Hippo pathway is reviewed specifically in the setting of sarcoma due to increased activation of this pathway in multiple subtypes. Role and efficacy of photodynamic therapy in other malignancies is also reviewed, with additional discussion of preclinical studies demonstrating synergistic effects of photodynamic therapy within current sarcoma standard of care treatment. Future investigations of the feasibility of incorporating verteporfin into sarcoma treatment are discussed. Abstract Sarcoma is a widely varied and devastating oncological subtype, with overall five-year survival of 65% that drops to 16% with the presence of metastatic disease at diagnosis. Standard of care for localized sarcomas is predicated on local control with wide-local resection and radiation therapy, or, less commonly, chemotherapy, depending on tumor subtype. Verteporfin has the potential to be incorporated into this standard of care due to its unique molecular properties: inhibition of the upregulated Hippo pathway that frequently drives soft tissue sarcoma and photodynamic therapy-mediated necrosis due to oxidative damage. The initial anti-proliferative effect of verteporfin is mediated via binding and dissociation of YAP/TEAD proteins from the nucleus, ultimately leading to decreased cell proliferation as demonstrated in multiple in vitro studies. This effect has the potential to be compounded with use of photodynamic therapy to directly induce cellular necrosis with use of a clinical laser. Photodynamic therapy has been incorporated into multiple malignancies and has the potential to be incorporated into sarcoma treatment.
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Affiliation(s)
| | - Nicholas Scalora
- Department of Pathology, University of Iowa, Iowa City, IA 52242, USA; (N.S.); (K.G.); (M.T.)
| | - Keith Garcia
- Department of Pathology, University of Iowa, Iowa City, IA 52242, USA; (N.S.); (K.G.); (M.T.)
| | - Munir Tanas
- Department of Pathology, University of Iowa, Iowa City, IA 52242, USA; (N.S.); (K.G.); (M.T.)
| | - Fatima Toor
- Department of Electrical and Computer Engineering, University of Iowa Technology Institute, University of Iowa, Iowa City, IA 52242, USA;
| | - Benjamin Miller
- Department of Orthopedic Surgery, University of Iowa, Iowa City, IA 52242, USA;
| | - Bryan Allen
- Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA;
| | - Mohammed Milhem
- Division of Hematology, Oncology, and Blood & Marrow Transplant, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA;
| | - Varun Monga
- Division of Hematology, Oncology, and Blood & Marrow Transplant, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA;
- Correspondence: ; Tel.: +1-3-193-849-497
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Abstract
Malignant biliary obstruction (MBO), result of pancreatobiliary diseases is a challenging condition. Most patients with MBO are inoperable at the time of diagnosis, and the disease is poorly controlled using external-beam radiotherapy and chemotherapy. Biliary stent therapy emerged as a promising strategy for alleviating MBO and prolonging life. However, physicians find it difficult to determine the optimal type of biliary stent for the palliation of MBO. Here, we review the safety and efficacy of available biliary stents, used alone or in combination with brachytherapy, photodynamic therapy and advanced chemotherapeutics, in patients with pancreatobiliary malignancies and put forward countermeasures involving stent obstruction. Furthermore, 3D-printing stents and nanoparticle-loaded stents have broad application prospects for fabricating tailor-made biliary stents.
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38
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Nordmann NJ, Michael AP. 5-Aminolevulinic acid radiodynamic therapy for treatment of high-grade gliomas: A systematic review. Clin Neurol Neurosurg 2020; 201:106430. [PMID: 33360951 DOI: 10.1016/j.clineuro.2020.106430] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 12/09/2020] [Accepted: 12/10/2020] [Indexed: 01/22/2023]
Abstract
INTRODUCTION Radiodynamic therapy (RDT) involves administration of a radiosensitizing agent and its subsequent activation by ionizing radiation for destruction of neoplastic cells. MATERIALS AND METHODS A comprehensive evaluation of the literature was performed to review the history of RDT using porphyrins for solid tumors, the cellular mechanisms of action, immunomodulatory effects, and both preclinical and clinical studies for use in high-grade gliomas (HGGs). This manuscript was prepared in accordance with the PRISMA guidelines. RESULTS A total of 271 articles were considered for initial review. After removal of duplicates, articles not unrelated to specific topic, and exclusion of commentary articles, a total of 11 articles were subject to full analysis that included in vivo, in vitro, and human studies. Porphyrins such as 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) selectively accumulate in neoplastic cells and are currently used for fluorescent-guided surgical resection and photodynamic therapy (PDT) of HGG and other brain tumors. 5-ALA is also shown to act as a radiosensitizer by increasing oxidative stress in neoplastic cell mitochondria and enhancing the host immune response. Postoperative radiation therapy is currently the standard of care for treatment of HGG. CONCLUSION RDT remains a promising adjuvant therapy for HGGs and requires further investigation. Clinical trials of 5-ALA RDT for HGG are needed to evaluate the optimum timing, dosing and effectiveness.
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Affiliation(s)
- Nathan J Nordmann
- Division of Neurosurgery, Neuroscience Institute, Southern Illinois University School of Medicine. P.O. Box 19638, Springfield, IL, 62794-9638, United States
| | - Alex P Michael
- Division of Neurosurgery, Neuroscience Institute, Southern Illinois University School of Medicine. P.O. Box 19638, Springfield, IL, 62794-9638, United States.
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39
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Mu C, Wang W, Wang J, Gong C, Zhang D, Zhang X. Probe‐Free Direct Identification of Type I and Type II Photosensitized Oxidation Using Field‐Induced Droplet Ionization Mass Spectrometry. Angew Chem Int Ed Engl 2020. [DOI: 10.1002/ange.202010294] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Chaonan Mu
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Wei Wang
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Jie Wang
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Chu Gong
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Dongmei Zhang
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Xinxing Zhang
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
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40
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Simões JCS, Sarpaki S, Papadimitroulas P, Therrien B, Loudos G. Conjugated Photosensitizers for Imaging and PDT in Cancer Research. J Med Chem 2020; 63:14119-14150. [PMID: 32990442 DOI: 10.1021/acs.jmedchem.0c00047] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Early cancer detection and perfect understanding of the disease are imperative toward efficient treatments. It is straightforward that, for choosing a specific cancer treatment methodology, diagnostic agents undertake a critical role. Imaging is an extremely intriguing tool since it assumes a follow up to treatments to survey the accomplishment of the treatment and to recognize any conceivable repeating injuries. It also permits analysis of the disease, as well as to pursue treatment and monitor the possible changes that happen on the tumor. Likewise, it allows screening the adequacy of treatment and visualizing the state of the tumor. Additionally, when the treatment is finished, observing the patient is imperative to evaluate the treatment methodology and adjust the treatment if necessary. The goal of this review is to present an overview of conjugated photosensitizers for imaging and therapy.
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Affiliation(s)
- João C S Simões
- Institute of Chemistry, University of Neuchatel, Avenue de Bellevaux 51, CH-2000 Neuchatel, Switzerland.,BioEmission Technology Solutions, Alexandras Avenue 116, 11472 Athens, Greece
| | - Sophia Sarpaki
- BioEmission Technology Solutions, Alexandras Avenue 116, 11472 Athens, Greece
| | | | - Bruno Therrien
- Institute of Chemistry, University of Neuchatel, Avenue de Bellevaux 51, CH-2000 Neuchatel, Switzerland
| | - George Loudos
- BioEmission Technology Solutions, Alexandras Avenue 116, 11472 Athens, Greece
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41
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Casas A. Clinical uses of 5-aminolaevulinic acid in photodynamic treatment and photodetection of cancer: A review. Cancer Lett 2020; 490:165-173. [DOI: 10.1016/j.canlet.2020.06.008] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/02/2020] [Accepted: 06/05/2020] [Indexed: 02/08/2023]
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42
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Mu C, Wang W, Wang J, Gong C, Zhang D, Zhang X. Probe‐Free Direct Identification of Type I and Type II Photosensitized Oxidation Using Field‐Induced Droplet Ionization Mass Spectrometry. Angew Chem Int Ed Engl 2020; 59:21515-21519. [DOI: 10.1002/anie.202010294] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Indexed: 12/14/2022]
Affiliation(s)
- Chaonan Mu
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Wei Wang
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Jie Wang
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Chu Gong
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Dongmei Zhang
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
| | - Xinxing Zhang
- College of Chemistry Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Renewable Energy Conversion and Storage Center (ReCAST) Nankai University Tianjin 300071 China
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Guan Q, Wang GB, Zhou LL, Li WY, Dong YB. Nanoscale covalent organic frameworks as theranostic platforms for oncotherapy: synthesis, functionalization, and applications. NANOSCALE ADVANCES 2020; 2:3656-3733. [PMID: 36132748 PMCID: PMC9419729 DOI: 10.1039/d0na00537a] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 07/15/2020] [Indexed: 05/08/2023]
Abstract
Cancer nanomedicine is one of the most promising domains that has emerged in the continuing search for cancer diagnosis and treatment. The rapid development of nanomaterials and nanotechnology provide a vast array of materials for use in cancer nanomedicine. Among the various nanomaterials, covalent organic frameworks (COFs) are becoming an attractive class of upstarts owing to their high crystallinity, structural regularity, inherent porosity, extensive functionality, design flexibility, and good biocompatibility. In this comprehensive review, recent developments and key achievements of COFs are provided, including their structural design, synthesis methods, nanocrystallization, and functionalization strategies. Subsequently, a systematic overview of the potential oncotherapy applications achieved till date in the fast-growing field of COFs is provided with the aim to inspire further contributions and developments to this nascent but promising field. Finally, development opportunities, critical challenges, and some personal perspectives for COF-based cancer therapeutics are presented.
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Affiliation(s)
- Qun Guan
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University Jinan 250014 P. R. China
| | - Guang-Bo Wang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University Jinan 250014 P. R. China
| | - Le-Le Zhou
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University Jinan 250014 P. R. China
| | - Wen-Yan Li
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University Jinan 250014 P. R. China
| | - Yu-Bin Dong
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University Jinan 250014 P. R. China
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Krupka M, Bartusik-Aebisher D, Strzelczyk N, Latos M, Sieroń A, Cieślar G, Aebisher D, Czarnecka M, Kawczyk-Krupka A, Latos W. The role of autofluorescence, photodynamic diagnosis and Photodynamic therapy in malignant tumors of the duodenum. Photodiagnosis Photodyn Ther 2020; 32:101981. [PMID: 32882405 DOI: 10.1016/j.pdpdt.2020.101981] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Revised: 07/12/2020] [Accepted: 08/24/2020] [Indexed: 02/07/2023]
Abstract
This article presents the current state of knowledge and a review of the literature in terms of the prevalence, etiopathogenesis, differential diagnosis, management, prognosis, and treatment of malignant tumors of the duodenum. The role of autofluorescence and photodynamic diagnosis as an emerging treatment method for rarely o ccurring duodenal malignant neoplasms .. We selected publications which can be found in databases such as The National Center for Biotechnology Information, U.S. National Library of Medicine (PubMed), The American Chemical Society, The American Association of Pharmaceutical Sciences and The American Society for Photobiology and The Canada Institute for Scientific and Technical Information.
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Affiliation(s)
- Magdalena Krupka
- Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego 15, 41-902, Bytom, Poland.
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Faculty of Medicine, University of Rzeszów, Kopisto 2A, 35-310, Rzeszów, Poland.
| | - Natalia Strzelczyk
- Department of Internal Medicine, 11 Listopada 5E, 42-100, Kłobuck, Poland.
| | - Magdalena Latos
- Silesian Centre for Heart Disease in Zabrze, Marii Curie Skłodowskiej 9, 41-800 Zabrze, Poland.
| | - Aleksander Sieroń
- Jan Długosz University in Częstochowa, Waszyngtona 4/8, 42-200, Częstochowa, Poland.
| | - Grzegorz Cieślar
- Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego 15, 41-902, Bytom, Poland.
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Faculty of Medicine, University of Rzeszów, Kopisto 2A, 35-310, Rzeszów, Poland.
| | - Magdalena Czarnecka
- Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego 15, 41-902, Bytom, Poland.
| | - Aleksandra Kawczyk-Krupka
- Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego 15, 41-902, Bytom, Poland.
| | - Wojciech Latos
- Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, Batorego 15, 41-902, Bytom, Poland.
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Akter S, Saito S, Inai M, Honda N, Hazama H, Nishikawa T, Kaneda Y, Awazu K. Efficient photodynamic therapy against drug-resistant prostate cancer using replication-deficient virus particles and talaporfin sodium. Lasers Med Sci 2020; 36:743-750. [PMID: 32592133 DOI: 10.1007/s10103-020-03076-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 06/16/2020] [Indexed: 10/24/2022]
Abstract
To enhance the potency of photosensitizer, we developed a novel photosensitizer, Laserphyrin®-HVJ-E (L-HVJ-E), by incorporating talaporfin sodium (Laserphyrin®, Meiji Seika Pharma) into hemagglutinating virus of Japan envelope (HVJ-E). In this study, we examined the optimal Laserphyrin® concentration for preparation of Laserphyrin®-HVJ-E which had photocytotoxicity and maintained direct cytotoxicity derived from HVJ-E. Then, potency of Laserphyrin®-HVJ-E and Laserphyrin® were compared in vitro using castration-resistant prostate cancer cell line (PC-3). A laser diode (L660P120, Thorlabs, USA) with a wavelength of 664 nm was used for light activation of Laserphyrin®, which corresponds to an absorption peak of Laserphyrin® and provides a high therapeutic efficiency. The photocytotoxicity and direct cytotoxicity of Laserphyrin®-HVJ-E prepared using various Laserphyrin® concentrations were evaluated using PC-3 cell in vitro. We categorized the treatment groups as Group 1: 50 μL of D-MEM treatment group, Group 2: HVJ-E treatment group, Group 3: Laserphyrin®-HVJ-E treatment group, and Group 4: Laserphyrin® treatment group. Group 3 was subjected to different concentrations of Laserphyrin®-HVJ-E suspension, and all groups were subjected to different incubation periods (24, 48 h), (30 min, 1 h, or 3 h,) respectively, without and after PDT. Laserphyrin®-HVJ-E prepared using 15 mM Laserphyrin® had high photocytotoxicity and maintained HVJ-E's ability to induce direct cytotoxicity. Therapeutic effect of Laserphyrin®-HVJ-E was substantially equivalent to that of Laserphyrin® alone even at half Laserphyrin® concentration. By utilizing Laserphyrin®-HVJ-E, PDT could be performed with lower Laserphyrin® concentration. In addition, Laserphyrin®-HVJ-E showed higher potency than Laserphyrin® by combining cytotoxicities of HVJ-E and PDT.
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Affiliation(s)
- Sharmin Akter
- Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. .,Department of Physiology, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh.
| | - Sachiko Saito
- Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Mizuho Inai
- Graduate School of Frontier Biosciences, Osaka University, 1-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Norihiro Honda
- Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.,Institute for Academic Initiatives, Osaka University, 1-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hisanao Hazama
- Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tomoyuki Nishikawa
- Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yasufumi Kaneda
- Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kunio Awazu
- Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.,Graduate School of Frontier Biosciences, Osaka University, 1-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.,Global Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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Montaseri H, Kruger CA, Abrahamse H. Review: Organic nanoparticle based active targeting for photodynamic therapy treatment of breast cancer cells. Oncotarget 2020; 11:2120-2136. [PMID: 32547709 PMCID: PMC7275783 DOI: 10.18632/oncotarget.27596] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 04/27/2020] [Indexed: 12/27/2022] Open
Abstract
Targeted Photodynamic therapy (TPDT) is a non-invasive and site-specific treatment modality, which has been utilized to eradicate cancer tumour cells with photoactivated chemicals or photosensitizers (PSs), in the presence of laser light irradiation and molecular tissue oxygen. Breast cancer is the commonest cancer among women worldwide and is currently treated using conventional methods such as chemotherapy, radiotherapy and surgery. Despite the recent advancements made in PDT, poor water solubility and non-specificity of PSs, often affect the overall effectivity of this unconventional cancer treatment. With respect to conventional PS obstacles, great strides have been made towards the application of targeted nanoparticles in PDT to resolve these limitations. Therefore, this review provides an overview of scientific peer reviewed published studies in relation to functionalized organic nanoparticles (NPs) for effective TPDT treatment of breast cancer over the last 10 years (2009 to 2019). The main aim of this review is to highlight the importance of organic NP active based PDT targeted drug delivery systems, to improve the overall biodistribution of PSs in breast cancer tumour's.
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Affiliation(s)
- Hanieh Montaseri
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa
| | - Cherie Ann Kruger
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa
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León D, Buchegger K, Silva R, Riquelme I, Viscarra T, Mora-Lagos B, Zanella L, Schafer F, Kurachi C, Roa JC, Ili C, Brebi P. Epigallocatechin Gallate Enhances MAL-PDT Cytotoxic Effect on PDT-Resistant Skin Cancer Squamous Cells. Int J Mol Sci 2020; 21:ijms21093327. [PMID: 32397263 PMCID: PMC7247423 DOI: 10.3390/ijms21093327] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 01/18/2020] [Accepted: 01/20/2020] [Indexed: 02/06/2023] Open
Abstract
Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions.
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Affiliation(s)
- Daniela León
- Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional—Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (D.L.); (K.B.); (T.V.); (B.M.-L.); (L.Z.)
| | - Kurt Buchegger
- Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional—Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (D.L.); (K.B.); (T.V.); (B.M.-L.); (L.Z.)
- Department of Basic Sciences, School of Medicine, Universidad de La Frontera, Temuco 4811230, Chile
| | - Ramón Silva
- Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud. Universidad Autónoma de Chile, Temuco 4810101, Chile; (R.S.); (I.R.)
| | - Ismael Riquelme
- Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud. Universidad Autónoma de Chile, Temuco 4810101, Chile; (R.S.); (I.R.)
| | - Tamara Viscarra
- Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional—Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (D.L.); (K.B.); (T.V.); (B.M.-L.); (L.Z.)
| | - Bárbara Mora-Lagos
- Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional—Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (D.L.); (K.B.); (T.V.); (B.M.-L.); (L.Z.)
| | - Louise Zanella
- Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional—Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (D.L.); (K.B.); (T.V.); (B.M.-L.); (L.Z.)
| | - Fabiola Schafer
- Department of Medical Specialties, School of Medicine, Universidad de La Frontera, Temuco 4811230, Chile;
| | - Cristina Kurachi
- São Carlos Institute of Physics, University of São Paulo (USP), P.O. Box 369, São Carlos 13560-970, São Paulo, Brazil;
| | - Juan Carlos Roa
- Department of Pathology, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile;
| | - Carmen Ili
- Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional—Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (D.L.); (K.B.); (T.V.); (B.M.-L.); (L.Z.)
- Correspondence: (C.I.); (P.B.); Tel.: +56-45-2-596693 (C.I.); +56-45-2-596583 (P.B.)
| | - Priscilla Brebi
- Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional—Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (D.L.); (K.B.); (T.V.); (B.M.-L.); (L.Z.)
- Correspondence: (C.I.); (P.B.); Tel.: +56-45-2-596693 (C.I.); +56-45-2-596583 (P.B.)
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Maytin EV, Hasan T. Vitamin D and Other Differentiation-promoting Agents as Neoadjuvants for Photodynamic Therapy of Cancer. Photochem Photobiol 2020; 96:529-538. [PMID: 32077114 PMCID: PMC7384449 DOI: 10.1111/php.13230] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Accepted: 12/12/2019] [Indexed: 12/30/2022]
Abstract
The efficacy of photodynamic therapy (PDT) using aminolevulinic acid (ALA), which is preferentially taken up by cancerous cells and converted to protoporphyrin IX (PpIX), can be substantially improved by pretreating the tumor cells with vitamin D (Vit D). Vit D is one of several "differentiation-promoting agents" that can promote the preferential accumulation of PpIX within the mitochondria of neoplastic cells, making them better targets for PDT. This article provides a historical overview of how the concept of using combination agents ("neoadjuvants") for PDT evolved, from initial discoveries about neoadjuvant effects of methotrexate and fluorouracil to later studies to determine how vitamin D and other agents actually work to augment PDT efficacy. While this review focuses mainly on skin cancer, it includes a discussion about how these concepts may be applied more broadly toward improving PDT outcomes in other types of cancer.
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Affiliation(s)
- Edward V Maytin
- Departments of Dermatology and Biomedical Engineering, Cleveland Clinic, Cleveland, OH
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
| | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
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Sorrin AJ, Ruhi MK, Ferlic NA, Karimnia V, Polacheck WJ, Celli JP, Huang HC, Rizvi I. Photodynamic Therapy and the Biophysics of the Tumor Microenvironment. Photochem Photobiol 2020; 96:232-259. [PMID: 31895481 PMCID: PMC7138751 DOI: 10.1111/php.13209] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 11/27/2019] [Indexed: 02/07/2023]
Abstract
Targeting the tumor microenvironment (TME) provides opportunities to modulate tumor physiology, enhance the delivery of therapeutic agents, impact immune response and overcome resistance. Photodynamic therapy (PDT) is a photochemistry-based, nonthermal modality that produces reactive molecular species at the site of light activation and is in the clinic for nononcologic and oncologic applications. The unique mechanisms and exquisite spatiotemporal control inherent to PDT enable selective modulation or destruction of the TME and cancer cells. Mechanical stress plays an important role in tumor growth and survival, with increasing implications for therapy design and drug delivery, but remains understudied in the context of PDT and PDT-based combinations. This review describes pharmacoengineering and bioengineering approaches in PDT to target cellular and noncellular components of the TME, as well as molecular targets on tumor and tumor-associated cells. Particular emphasis is placed on the role of mechanical stress in the context of targeted PDT regimens, and combinations, for primary and metastatic tumors.
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Affiliation(s)
- Aaron J. Sorrin
- Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA
| | - Mustafa Kemal Ruhi
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC and North Carolina State University, Raleigh, NC, 27599, USA
| | - Nathaniel A. Ferlic
- Department of Electrical and Computer Engineering, University of Maryland, College Park, MD, 20742, USA
| | - Vida Karimnia
- Department of Physics, College of Science and Mathematics, University of Massachusetts at Boston, Boston, MA, 02125, USA
| | - William J. Polacheck
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC and North Carolina State University, Raleigh, NC, 27599, USA
- Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA
| | - Jonathan P. Celli
- Department of Physics, College of Science and Mathematics, University of Massachusetts at Boston, Boston, MA, 02125, USA
| | - Huang-Chiao Huang
- Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Imran Rizvi
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC and North Carolina State University, Raleigh, NC, 27599, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA
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Cheng Y, Kong X, Chang Y, Feng Y, Zheng R, Wu X, Xu K, Gao X, Zhang H. Spatiotemporally Synchronous Oxygen Self-Supply and Reactive Oxygen Species Production on Z-Scheme Heterostructures for Hypoxic Tumor Therapy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2020; 32:e1908109. [PMID: 32022983 DOI: 10.1002/adma.201908109] [Citation(s) in RCA: 112] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Indexed: 06/10/2023]
Abstract
Photodynamic therapy (PDT) efficacy has been severely limited by oxygen (O2 ) deficiency in tumors and the electron-hole separation inefficiency in photosensitizers, especially the long-range diffusion of O2 toward photosensitizers during the PDT process. Herein, novel bismuth sulfide (Bi2 S3 )@bismuth (Bi) Z-scheme heterostructured nanorods (NRs) are designed to realize the spatiotemporally synchronous O2 self-supply and production of reactive oxygen species for hypoxic tumor therapy. Both narrow-bandgap Bi2 S3 and Bi components can be excited by a near-infrared laser to generate abundant electrons and holes. The Z-scheme heterostructure endows Bi2 S3 @Bi NRs with an efficient electron-hole separation ability and potent redox potentials, where the hole on the valence band of Bi2 S3 can react with water to supply O2 for the electron on the conduction band of Bi to produce reactive oxygen species. The Bi2 S3 @Bi NRs overcome the major obstacles of conventional photosensitizers during the PDT process and exhibit a promising phototherapeutic effect, supplying a new strategy for hypoxic tumor elimination.
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Affiliation(s)
- Yan Cheng
- Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, China
| | - Xiangpeng Kong
- College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330000, Jiangxi, China
| | - Yun Chang
- Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, China
| | - Yanlin Feng
- Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, China
- University of Science and Technology of China, Hefei, 230026, Anhui, China
| | - Runxiao Zheng
- Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, China
- University of Science and Technology of China, Hefei, 230026, Anhui, China
| | - Xiaqing Wu
- Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, China
- University of Science and Technology of China, Hefei, 230026, Anhui, China
| | - Keqiang Xu
- Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, China
- University of Science and Technology of China, Hefei, 230026, Anhui, China
| | - Xingfa Gao
- College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330000, Jiangxi, China
| | - Haiyuan Zhang
- Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, China
- University of Science and Technology of China, Hefei, 230026, Anhui, China
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