Photoactivatable Cisplatin-Combretastatin-BODIPY Pt(IV) Prodrug for Dual-Action Light-Controlled Chemotherapy
Herein, we designed, synthesized, and studied the activity of a novel dual-action red light-activatable Pt-(IV) prodrug <b>BDP-Pt-CA4</b> with a BODIPY fluorophore and CA4 in axial positions, capable of light-controlled release of two chemotherapeutic drugs: cisplatin and combretastatin A4 (CA4). To the best of our knowledge, this is the first example of a dual-action photoactive Pt-(IV)-CA4 prodrug that releases two antiproliferative agents upon red light irradiation. The aim of this work was to demonstrate light-induced release of CA4 and cisplatin from the prodrug, occurring strictly on demand to reduce the overall toxicity of the drug and minimize the damaging effect on normal tissues. In addition to <i>in vitro</i> evidence of light-induced release of two chemotherapeutic agents, a controllable release of both drugs inside cancer cells was also proven. For the first time, a light-induced release of the tubulin polymerization inhibitor from a photoactivatable prodrug was observed via quantification of subtle changes in the mechanistic properties of cell surfaces via single-cell low-stress scanning ion conductance microscopy (SICM). Our results clearly demonstrate a perspective for photoactive Pt-(IV) prodrugs, confirming an ability to release the platinum agent "on demand", and to act as light-controlled dual-action chemotherapy.
Authors
- Dmitry A. Skvortsov (ORCID: https://orcid.org/0000-0001-8336-8596)
- Вита Н. Никитина (ORCID: https://orcid.org/0000-0001-6821-6949)
- Tatiana V. Egorova (ORCID: https://orcid.org/0000-0002-3346-3242)
- Alexander N. Vaneev (ORCID: https://orcid.org/0000-0001-8201-8498)
- Dmitry A. Bunin
- Anna Bubley
- Alexander S. Erofeev (ORCID: https://orcid.org/0000-0002-6631-821X)
- Elena Kimovna Beloglazkina (ORCID: https://orcid.org/0000-0001-6796-8241)
- Alexander G. Martynov (ORCID: https://orcid.org/0000-0002-2192-7134)
- И. А. Родин (ORCID: https://orcid.org/0000-0002-0588-6870)
- Roman Akasov (ORCID: https://orcid.org/0000-0001-6486-8114)
- Василий Колмогоров (ORCID: https://orcid.org/0000-0002-7135-8910)
- Vugara V. Mamed‐Nabizade (ORCID: https://orcid.org/0000-0001-8460-4685)
- Mikhail F. Vokuev (ORCID: https://orcid.org/0000-0002-1733-4969)
- Olga Olegovna Krasnovskaya (ORCID: https://orcid.org/0000-0002-4948-2747)
- Yuri K. Grishin (ORCID: https://orcid.org/0000-0001-7709-5245)
- Georgy L. Karetnikov (ORCID: https://orcid.org/0000-0002-0577-8968)
- Daria A. Ipatova
- Petr V. Gorelkin (ORCID: https://orcid.org/0000-0002-4860-9013)
- Daniil V. Spector (ORCID: https://orcid.org/0000-0002-2726-2671)
- Yulia A. Isaeva
- Vitaly A. Roznyatovsky
Institutions
- National University of Science and Technology (RU)
- Moscow State Pedagogical University (RU)
- Lomonosov Moscow State University (RU)
- Frumkin Institute of Physical Chemistry and Electrochemistry Russian Academy of Sciences (RU)
Publication Details
- Journal
- ACS Pharmacology & Translational Science
- Published
- 2025-08-05
- DOI
- https://doi.org/10.1021/acsptsci.5c00442
- Citations
- 2
- Primary Topic
- Advanced biosensing and bioanalysis techniques
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Russian Science Foundation
- Lomonosov Moscow State University