Green Light Activated Dual-Action Pt(IV) Prodrug with Enhanced PDT Activity

被引：0

作者：

Spector, Daniil ^{[1
]}

Bykusov, Vladislav ^{[1
]}

Isaeva, Yulia ^{[2
,3
]}

Akasov, Roman ^{[2
,3
]}

Zharova, Anastasia ^{[1
]}

Rodin, Igor ^{[1
]}

Vokuev, Mikhail ^{[1
]}

Grishin, Yuri ^{[1
]}

Nikitina, Vita ^{[1
]}

Martynov, Alexander ^{[4
]}

Kuzmin, Vladimir ^{[5
]}

Beloglazkina, Elena ^{[1
]}

Krasnovskaya, Olga ^{[1
]}

机构：

[1] Lomonosov Moscow State Univ, Chem Dept, Leninskie Gory 1, Moscow 119991, Russia

[2] IM Sechenov First Moscow State Med Univ, Trubetskaya 8-2, Moscow 119991, Russia

[3] Moscow Pedag State Univ, Malaya Pirogovskaya Str 1, Moscow 119435, Russia

[4] Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Leninskii Pr 31,Bldg 4, Moscow 119071, Russia

[5] Russian Acad Sci, Emanuel Inst Biochem Phys, Kosygina Str,B 4, Moscow 119334, Russia

来源：

CHEMMEDCHEM | 2025年

关键词：

BODIPY; cisplatin; PDT; Prodrug; photoactivation; ASCORBIC-ACID; BASIS-SETS; BODIPY; OXALIPLATIN; DELIVERY; DESIGN; AGENTS;

D O I：

10.1002/cmdc.202400786

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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/cm2. The investigation of the photoreduction mechanism of GreenPt prodrug using DFT modeling and Delta G0 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.

引用

页数：14

共 80 条

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