Nanoformulation of the Photoactive Cisplatin Prodrug for Combined Photothermal Therapy and Bioimaging

• Published in: ACS applied nano materials 2024-11, Vol.7 (22), p.25603-25618
• Main Authors: Spector, Daniil V., Bykusov, Vladislav, Zharova, Anastasia, Kuzmichev, Ilia, Isaeva, Yulia A., Khaydukov, Evgeny V., Trifanova, Ekaterina, Stepanov, Maxim, Erofeev, Alexander S., Gorelkin, Petr, Kuanaeva, Regina, Nikitina, Vita N., Dubenskii, Alexander, Maksimova, Yulia, Skvortsov, Dmitry Aleksandrovich, Ipatova, Daria, Rodin, Igor A., Vokuev, Mikhail F., Martynov, Alexander G., Bunin, Dmitry, Pokrovsky, Vadim S., Babayeva, Gulalek, Uskova, Tamara, Abakumov, Maxim A., Beloglazkina, Elena K., Akasov, Roman A., Krasnovskaya, Olga O.
• Format: Article
• Language: English
• ISSN: 2574-0970; 2574-0970
• DOI: 10.1021/acsanm.4c04680

Cancer phototheranostics is a new mode of precise treatment based on fluorescent and photothermal imaging (PTI), combined with photodynamic (PDT) and photothermal therapy (PTT). Herein, we designed a photoactive Pt­(IV) prodrug Pt-1 with BODIPY-based triplet photosensitizer as an axial ligand that exhibits cytotoxic effects through both PDT and photoactivated chemotherapy (PACT). Based on the Pt-1 prodrug, we developed a multifunctional theranostic nanoplatform Pt-NPs with combined PDT/PTT activity, capable of light-induced cisplatin release and suitable for photothermal and fluorescent tumor imaging. Upon 660 nm laser irradiation, Pt-NPs efficiently causes regional hyperpyrexia, with a photothermal conversion efficiency of 42.1%. Synergistically, Pt-NPs acts as a PDT type I agent. In vivo PTI studies have shown bright fluorescence of the CT-26 tumor after intravenous injection of Pt-NPs, indicating accumulation and retention of Pt-NPs in the tumor. This is the first example of PTT/PDT-active NPs based on Pt­(IV) prodrug capable of photoinduced release of cisplatin. This strategy of the synergistic light-induced PDT/PTT/PACT action of Pt-NPs provides a new platform for the future design of phototheranostic agents for enhanced tumor treatment and imaging.