Photothermally reinforced chemodynamic therapy in the treatment of osteosarcoma by polydopamine-modified, copper peroxide loaded ZIF8 nanoparticles

Chemodynamic therapy (CDT) has played an important role in osteosarcoma (OS) treatment. However, the insufficient content of endogenous H 2 O 2 and high expression of glutathione (GSH) in tumor tissues limit the antitumor efficacy of CDT. In this work, we developed polydopamine (PDA) coated and CuO 2 NPs loaded ZIF8 nanoparticles (CuO 2 @ZIF8@PDA NPs) for thermally reinforced CDT treatment of OS. The CuO 2 @ZIF8@PDA NPs exhibited excellent stability in neutral solutions while degraded in weakly acidic environments to generate hydrogen peroxide (H 2 O 2 ) and Cu 2+ . Cu 2+ consumes GSH in tumor tissues to generate Cu + . Both Cu 2+ and Cu + catalyzed the decomposition of H 2 O 2 , triggering a Fenton-like reaction to produce hydroxyl radicals (•OH). The PDA coating endowed the nanosystem with photothermal conversion capabilities under near-infrared laser irradiation, further promoting the generation of •OH, and inducing tumor cell death. In vitro experiments demonstrated that CuO 2 @ZIF8@PDA NPs exhibited significant toxicity towards K7M2 cells while remaining non-toxic to normal cells. In vivo studies revealed that under 808 nm laser irradiation, CuO 2 @ZIF8@PDA NPs exhibited stronger killing ability against K7M2 cells than CuO 2 @ZIF8@PDA NPs alone. This system, which combines GSH depletion, intratumoral H 2 O 2 self-generation, and photothermally enhanced CDT, holds great promise for playing a pivotal role in the treatment of osteosarcoma.