PARP inhibitors diminish DNA damage repair for the enhancement of tumor photodynamic therapy |
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| Affiliation: | 1. College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China;2. Center for Laboratory Medicine, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People''s Hospital (Affiliated People''s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, China;3. Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China;4. Hangzhou Chinese Academy of Sciences-Hangzhou Medical College, Advanced Medical Technology Institute, Hangzhou 310014, China;5. Joint Centre of Translational Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China;1. Department of Endodontics, Faculty of Dentistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran;2. Iranian Center for Endodontic Research, Research Institute of Dental Sciences, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, Iran;3. Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran;1. Community Division, Department of Preventive Dental Sciences, College of Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia;2. Department of General Dental Practice, Faculty of Dentistry, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait;3. Department of Oral Medicine and Radiology, Sharavathi Dental College and Hospital, Shivamogga, Karnataka 577204, India;4. Department of Oral Medicine and Radiology, Faculty of Dentistry, Levy Mwanawasa Medical University (LMMU), Ministry of Health, Lusaka, 10101, Zambia;5. Department of Preventive Dental Sciences, College of Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia;1. Department of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China;2. Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, China;3. Academician (Expert) Workstation of Sichuan Province, Luzhou 646000, China;4. Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China;1. Faculty of Health Sciences, Izmir Katip Çelebi University, Izmir Kâtip Çelebi Üniversitesi Balatçık Kampüsü, Çiğli, İzmir 35620, Turkey;2. Faculty of Pharmacy, Department of Pharmaceutical Microbiology, Ege University, Turkey;3. Faculty of Engineering, Department of Biomedical Engineering, İzmir Katip Çelebi University, Turkey;4. Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ege University, Turkey;6. Faculty of Medicine, Department of Microbiology, İzmir Katip Çelebi University, Turkey;1. Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, Osaka, 565-0871, Japan;2. Graduate School of Medicine, Osaka Metropolitan University, 1-4-3, Asahimachi, Abeno-ku, Osaka, 545-8585, Japan;3. Global Center for Medical Engineering and Informatics, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan |
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| Abstract: | Pancreatic cancer is a lethal malignancy and only around 4% of patients will live 5 years post-diagnosis. Photodynamic therapy (PDT) is a promising strategy for treating malignant tumors because of its high selectivity. Through the colocalization of light, oxygen and photosensitizer, a large number of reactive oxygen species (ROS) are generated under excitation at a specific wavelength of a laser, which can induce DNA damage and destroy cancer cells. However, the repair mechanism of cell will repair part of the damaged DNA, which could reduce the efficiency of PDT. The poly (ADP-Ribose) polymerase (PARP) plays a wide and multifaceted role in the cellular response to DNA damage, with growing evidence for participation in multiple pathways of DNA damage repair and genome maintenance. Cells require PARP to resolve single-strand DNA breaks (SSBs) induced by chemotherapy agents. Its inhibition is thought to result in the accumulation of damage in DNA, which may eventually lead to cell death. The combination therapy of PDT and PARP inhibitors may benefit patients. In this study, we design and synthesize a zeolitic imidazolate framework-8 (ZIF-8) to co-deliver DNA damaging agent Chlorin e6 (Ce6) and PARP inhibitor Olaparib (Ola). Ce6 and Ola demonstrate strong synergistic actions, providing a novel approach for the treatment of pancreatic cancer. |
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| Keywords: | Photodynamic therapy |
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