Lei Siyun, Ge Feihang, Lin Minghao, Wang Xueli, Shen Jinglan, Yang Yimin, Deng Junjie, Wang Zhen, Wang Jianwei, Li Kaiqiang
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China; 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.
Hangzhou Chinese Academy of Sciences-Hangzhou Medical College, Advanced Medical Technology Institute, Hangzhou 310014, China.
Photodiagnosis Photodyn Ther. 2022 Dec;40:103058. doi: 10.1016/j.pdpdt.2022.103058. Epub 2022 Aug 6.
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.
胰腺癌是一种致命的恶性肿瘤，只有约4%的患者在确诊后能活5年。光动力疗法（PDT）因其高选择性，是一种治疗恶性肿瘤的有前景的策略。通过光、氧和光敏剂的共定位，在特定波长激光激发下会产生大量活性氧（ROS），可诱导DNA损伤并破坏癌细胞。然而，细胞的修复机制会修复部分受损DNA，这可能会降低PDT的效率。聚（ADP - 核糖）聚合酶（PARP）在细胞对DNA损伤的反应中发挥广泛而多方面的作用，越来越多的证据表明其参与DNA损伤修复和基因组维持的多种途径。细胞需要PARP来解决化疗药物诱导的单链DNA断裂（SSB）。其抑制作用被认为会导致DNA损伤的积累，最终可能导致细胞死亡。PDT与PARP抑制剂的联合治疗可能使患者受益。在本研究中，我们设计并合成了沸石咪唑酯骨架-8（ZIF-8），用于共递送DNA损伤剂二氢卟吩e6（Ce6）和PARP抑制剂奥拉帕利（Ola）。Ce6和Ola表现出强大的协同作用，为胰腺癌治疗提供了一种新方法。
