Photothermal controlled oxygen self-supplying “nano-bombs” via lysosome burst for transcytosis delivery and anti-tumor therapy

Abstract The delivery efficiency of less than 1% has severely limited the clinical application of nanomedicines, and exosome-mediated transcytosis provides a new view for improving the delivery of nanomedicines to tumor tissues. We proposed a novel “nano-bombs” strategy for rapid tumor penetration and efficiently catalyze anti-tumor therapy, and the nano-bombs (PFH@Ag@Ch-I) were composed of Ag silver nanocages (Ag NCs) loaded with perfluorohexane (PFH), chitosan (Ch) and indocyanine green (ICG). The PFH@Ag@Ch-I entered to lysosomes of tumor cells, and the temperature was increased to ~50°C by Ag NCs-triggered photothermal therapy under near-infrared light. Rapid phase transitions of PFH with oxygen increased the internal pressure of “nano-bombs” to burst lysosomes, and dysfunction of lysosomes directly led to exosome secretion increase. The “nano-bombs” encapsulated by exosomes were transmitted to the deep layer of tumor, and the delivery efficiency was significantly enhanced (16.873 %ID g−1) compared with that of Ag@Ch-I (7.860 %ID g−1). Meanwhile, the Ag NCs shattered into a number of smaller silver nanoparticles with catalytic ability for hydrogen peroxide to produce •OH for chemodynamic therapy. In addition, the O2 release improved hypoxic environments, which was reflected in up-regulation of HIF-1α, and enhanced reactive oxygen species for photodynamic therapy.