新型双功能核糖铂（IV）前药的光诱导还原
Photoinduced Reduction of Novel Dual-Action Riboplatin Pt(IV) Prodrug.
作者信息
Krasnovskaya Olga O, Akasov Roman A, Spector Daniil V, Pavlov Kirill G, Bubley Anna A, Kuzmin Vladimir A, Kostyukov Alexey A, Khaydukov Evgeny V, Lopatukhina Elena V, Semkina Alevtina S, Vlasova Kseniya Yu, Sypalov Sergey A, Erofeev Alexander S, Gorelkin Petr V, Vaneev Alexander N, Nikitina Vita N, Skvortsov Dmitrii A, Ipatova Daria A, Mazur Dmitrii M, Zyk Nikolay V, Sakharov Dmitry A, Majouga Alexander G, Beloglazkina Elena K
机构信息
Chemistry Department, Lomonosov Moscow State University, Leninskie Gory 1-3, Moscow 119991, Russia.
National University of Science and Technology (MISIS), Leninskiy Prospect 4, Moscow 119049, Russia.
出版信息
ACS Appl Mater Interfaces. 2023 Mar 15;15(10):12882-12894. doi: 10.1021/acsami.3c01771. Epub 2023 Feb 28.
Controlled photoreduction of Pt(IV) prodrugs is a challenging task due to the possibility of targeted light-controlled activation of anticancer agents without affecting healthy tissues. Also, a conjugation of photosensitizers and clinically used platinum drugs into one Pt(IV) prodrug allows combining photodynamic therapy and chemotherapy approaches into one molecule. Herein, we designed the cisplatin-based Pt(IV) prodrug Riboplatin with tetraacetylriboflavin in the axial position. A novel Pt(IV) prodrug is able to act both as a photodynamic therapy (PDT) agent through the conversion of ground-state O to excited-state O and as an agent of photoactivated chemotherapy (PACT) through releasing of cisplatin under gentle blue light irradiation, without the requirement of a reducing agent. The light-induced behavior of Riboplatin was investigated using an electrochemical sensor in MCF-7 tumor spheroids. Photocontrolled cisplatin release and ROS generation were detected electrochemically in real time. This appears to be the first confirmation of simultaneous photoactivated release of anticancer drug cisplatin and ROS from a dual-action Pt(IV) prodrug observed from the inside of living tumor spheroids.
由于有可能在不影响健康组织的情况下实现抗癌药物的靶向光控激活，因此铂（IV）前药的可控光还原是一项具有挑战性的任务。此外，将光敏剂与临床使用的铂类药物偶联成一种铂（IV）前药，可将光动力疗法和化疗方法结合在一个分子中。在此，我们设计了轴向带有四乙酰核黄素的顺铂基铂（IV）前药Riboplatin。一种新型铂（IV）前药能够通过将基态氧转化为激发态氧而作为光动力疗法（PDT）药物发挥作用，并通过在柔和蓝光照射下释放顺铂而作为光活化化疗（PACT）药物发挥作用，无需还原剂。使用电化学传感器在MCF-7肿瘤球体中研究了Riboplatin的光诱导行为。通过电化学实时检测到了光控顺铂释放和活性氧生成。这似乎是首次从活肿瘤球体内部观察到双功能铂（IV）前药同时光活化释放抗癌药物顺铂和活性氧的证实。
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