A surface convertible nanoplatform with enhanced mitochondria targeted delivery for tumor photothermal therapy

Abstract Photothermal therapy emerges as a promising approach in antitumor treatment. A major challenge for conventional photothermal therapy is its unselective hyperthermia distribution within tumor tissues, which leads to detrimental effects on surrounding healthy tissues and compromised therapeutic effectiveness. In this study, a targeted photothermal delivery nanoplatform (P-D-CS-CNTs) was facilely fabricated by decoration of an acidity-labile polyethylene glycol (PEG) derivative onto chitosan nanoparticles encapsulating single-walled carbon nanotubes. P-D-CS-CNTs displayed a good stability in serum at normal physiological pH and convertibility of surface charges upon exposure to tumoral acidic pH, which was attributed to the acidity-triggered dePEGylation. The confocal laser scanning microscopic observations suggested that such surface-convertibility of nanoparticles facilitated tumor cell uptake, endo/lyososomal escape, and enhanced mitochondrial targeting. Furthermore, upon irradiation with an 808 nm laser, P-D-CS-CNTs could sabotage mitochondria with mild hyperthermia, which further induced the ROS burst from damaged mitochondria. The overdosed ROS ultimately resulted in mitochondrial damage and cell death. These findings indicate that the surface-convertible nanoplatform is promising for improved photothermal anticancer therapy.