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 H2O2 and high expression of glutathione (GSH) in tumor tissues limit the antitumor efficacy of CDT. In this work, we developed polydopamine (PDA) coated and CuO2 NPs loaded ZIF8 nanoparticles (CuO2@ZIF8@PDA NPs) for thermally reinforced CDT treatment of OS. The CuO2@ZIF8@PDA NPs exhibited excellent stability in neutral solutions while degraded in weakly acidic environments to generate hydrogen peroxide (H2O2) and Cu2+. Cu2+ consumes GSH in tumor tissues to generate Cu+. Both Cu2+ and Cu+ catalyzed the decomposition of H2O2, triggering a Fenton-like reaction to produce hydroxyl radicals (center dot OH). The PDA coating endowed the nanosystem with photothermal conversion capabilities under near-infrared laser irradiation, further promoting the generation of center dot OH, and inducing tumor cell death. In vitro experiments demonstrated that CuO2@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, CuO2@ZIF8@PDA NPs exhibited stronger killing ability against K7M2 cells than CuO2@ZIF8@PDA NPs alone. This system, which combines GSH depletion, intratumoral H2O2 self-generation, and photothermally enhanced CDT, holds great promise for playing a pivotal role in the treatment of osteosarcoma.