Cancer cell membrane camouflaged iridium complexes functionalized black-titanium nanoparticles for hierarchical-targeted synergistic NIR-II photothermal and sonodynamic therapy.

The diagnosis and treatment of cancer is one of the biggest medical challenges of the century. Despite significant improvements, there remains an urgent need for novel anticancer procedures. Among the most promising approaches, increasing attention has been devoted towards photothermal and sonodynamic therapy in which sensitizers are activated upon light/ultrasound radiation to generate a cytotoxic effect. While these methods have undoubtedly shown a high therapeutic success, these techniques are intrinsically limited. Herein, the functionalization of black-titanium nanoparticle with iridium complexes and cancer cell membranes in a nanoplatform for hierarchical targeted synergistic photothermal and sonodynamic cancer imaging and therapy is proposed. The particles showed to generate efficiently heat upon irradiation and catalytically form reactive oxygen species upon ultrasound radiation. The nanoparticle formulation demonstrated to selectively localize in the mitochondria as well as to preferentially accumulate in cancerous over non-cancerous cells as well as in the tumor inside a mouse model, presenting a hierarchical targeting strategy. Upon synergistic irradiation at 1064 nm and ultrasound radiation, the nanoparticles were able to act as an imaging agent and identify the tumor site with high spatial resolution as well as act as a therapeutic agent and completely eradicate a tumor inside a mouse model.