Near-Infrared Light-Responsive Nanosystem with Prolonged Circulation and Enhanced Penetration for Increased Photothermal and Photodynamic Therapy

It is still a challenge to optimize the tumor therapeutic efficacy via overcoming poor penetration and enhancing accumulation of nanomedicines simultaneously. Here, we developed a near-infrared (NIR) light-triggered disintegratable delivery system (Lipo@ICG@CuS) composed of thermosensitive liposome, photosensitizer indocyanine green (ICG), and ultrasmall copper sulfide nanoparticles (CuS NPs), where ICG was embedded in the lipid bilayer and CuS NPs were encapsulated into the cavity of the liposome, respectively. Upon being irradiated by an 808 nm NIR laser, the local temperature of Lipo@ICG@CuS NPs is increased significantly, because of the photothermal capability of the loaded CuS NPs, and subsequently induces the structural collapse of thermosensitive liposomes to release the ICG and CuS NPs. The in vitro and in vivo results indicated that the as-prepared Lipo@ICG@CuS NPs could considerably prompt the CuS NPs to penetrate and accumulate deeply in tumors and obtained distinguished antitumor efficacy by combinatorial photodynamic therapy (PDT) and photothermal therapy (PTT). The current study provides a new strategy for solving the inherent dilemma of the long blood circulation but poor penetration and accumulation of large-sized NPs, as well as the deep penetration but easy clearance of small-sized NPs during the tumor therapy of nanomedicines.