Sulfur Defect-Engineered Biodegradable Cobalt Sulfide Quantum Dot-Driven Photothermal and Chemodynamic Anticancer Therapy

Abstract

Chemodynamic therapy (CDT), as a powerful tumor therapeutic approach with low side effects and selective therapeutic efficiency, has gained much attention. However, the low intracellular content of H₂O₂ and the cellular bottleneck of low intracellular oxidative reaction rates at tumor sites have limited the antitumor efficacy of CDT. Herein, a series of sulfur-deficient engineered biodegradable cobalt sulfide quantum dots (CoS_x QDs) were constructed for improved synergistic photothermal- and hyperthermal-enhanced CDT of tumors through regulating the photothermal conversion efficiency (PCE) and Fenton-like activity. Through defect engineering, we modulated the PCE and promoted the Fenton catalytic capability of CoS_x QDs. With increasing defect sites, the Fenton-like activity improved to generate more toxic ^?OH, while the photothermal effect declined slightly. In light of above unique superiorities, the best synergistic effects of CoS_x QDs were obtained through comparing their PCE and catalytic activity by regulating the sulfur defect fraction degree in these QDs during the synthetic process. In addition, the ultrasmall size and biodegradation endowed QDs with the ability to be rapidly decomposed to ions that were easily excreted after therapy, thus reducing biogenic accumulation in the body with lowered systemic side effects. The in vitro/vivo results demonstrated that the photothermal- and hyperthermal-enhanced chemodynamic effect of CoS_x QDs can enable remarkable anticancer properties with favorable biocompatibility. In this study, the defect-driven mechanism for the photothermal-enhanced Fenton-like reaction provides a flexible strategy to deal with different treatment environments, holding great promise in developing a multifunctional platform for cancer treatment in the future.