Photoinduced Reduction of Novel Dual-Action Riboplatin Pt(IV) Prodrug

• Published in: ACS applied materials & interfaces Vol. 15; no. 10; pp. 12882 - 12894
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15.03.2023
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and Medical Applications of Materials and Interfaces; Cell Line, Tumor; Cisplatin - chemistry; Cisplatin - pharmacology; Platinum - chemistry; Prodrugs - chemistry; Prodrugs - pharmacology; Reactive Oxygen Species; PDT; controlled release; PACT; ROS; cisplatin; nanoelectrode; riboflavin; Pt(IV) prodrugs
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.3c01771

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 3O2 to excited-state 1O2 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.