Green Light Activated Dual‐Action Pt(IV) Prodrug with Enhanced PDT Activity
Daniil V. Spector, Vladislav Bykusov, Yulia A. Isaeva, Roman Akasov, A. Zharova, И. А. Родин, Mikhail F. Vokuev, Yuri K. Grishin, Вита Н. Никитина, Alexander G. Martynov, V. A. Kuz’min, Елена К. Белоглазкина, Olga O. Krasnovskaya
Abstract
Abstract Light induced release of cisplatin from Pt(IV) prodrugs is a promising tool for precise spatiotemporal control over the antiproliferative activity of Pt‐based chemotherapeutic drugs. A combination of light‐controlled chemotherapy (PACT) and photodynamic therapy (PDT) in one molecule has the potential to overcome crucial drawbacks of both Pt‐based chemotherapy and PDT via a synergetic effect. Herein we report green‐light‐activated Pt(IV) prodrug GreenPt with BODIPY‐based photosentitizer in the axial position with an incredible high light response and singlet oxygen generation ability. GreenPt demonstrated the ability to release cisplatin under low‐dose green light irradiation up to 1 J/cm 2 . The investigation of the photoreduction mechanism of GreenPt prodrug using DFT modeling and ΔG 0 PET estimation revealed that the anion‐radical formation and substituent photoinduced electron transfer from the triplet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light‐induced release of cisplatin. Green‐light‐activated BODIPY‐based photosentitizers 5 and 8 demonstrated outstanding photosensitizing properties with an extraordinary phototoxicity index (PI)>1300. GreenPt prodrug demonstrated gradual intracellular accumulation and light‐induced phototoxicity with PI>100, thus demonstrating dual action through light‐controlled release of both cisplatin and a potent BODIPY‐based photosensitizer.