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

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.