Cooperative Nanoparticle System for Photothermal Tumor Treatment without Skin Damage

How to ablate tumors without using skin-harmful high laser irradiance remains an ongoing challenge for photothermal therapy. Here, we achieve this with a cooperative nanosystem consisting of gold nanocage (AuNC) "activator" and a cationic mammalian-membrane-disruptive peptide, cTL, as photothermal antenna and anticancer agent, respectively. Specifically, this nanosystem is prepared by grafting cTL onto AuNC via a Au-S bond, followed by attachment of thiolated polyethylene glycol (PEG) for stealth effects. Upon NIR irradiation at skin-permissible dosage, the resulting cTL/PEG-AuNC nanoparticle effectively ablates both irradiated and nonirradiated cancer cells, likely owing to cTL being responsively unleashed by intracellular thiols exposed to cTL/PEG-AuNC via membrane damage initiated by AuNC's photothermal effects and deteriorated by the as-released cTL. When administered systematically in a mouse model, cTL/PEG-AuNC populates tumors through their porous vessels and effectively destroys them without damaging skin.