A multifunctional nanocatalyst based on ultra-fluorescent carbon quantum dots for cascade enzymatic activity and stimuli-responsive chemotherapy of cancer

Clinical studies have switched from monotherapy to multimodal therapy due to the intricacy, multiplicity, and unpredictability of malignant tumors. In this work, we report one-pot microwave synthesis of highly fluorescent copper, nitrogen, and sulfur-doped carbon quantum dots (Cu,N,S-CQDs) with superior quantum yield (84%) and enhanced peroxidase-like activity. Then, Cu,N,S-CQDs was further biofunctionalized with glucose oxidase (GOx) and camptothecin (CPT) to form a multifunctional Cu,N,S-CQDs@GOx/CPT (CuCGC) nanocatalysts. The release of Cu2+ and S2− ions from CuCGC were promoted under acidic condition and catalyze the productions of hydroxyl (•OH) radical and H2S gas for chemodynamic (CDT) and gas (GT) therapy of cancer. Besides the CDT and GT effects, CuCGC also stimulates the breakdown of glucose into gluconic acid and peroxide solution for starvation therapy (ST) and ST-guided self-supplied CDT. CuCGC produce large quantities of reactive oxygen species (ROS) in the presence of H2O2 and glucose for enhanced cancer therapy via CDT and ST-guided CDT mechanisms. Interestingly, CuCGC nanocatalysts demonstrates ROS-responsive CPT release upon activation with H2O2 and glucose by CDT and ST-guided CDT, with about 66% of drug release was achieved in this study. In vitro analysis confirmed that our material reveals better biocompatibility towards cancer cells and caused substantial cell damage upon activation with H2O2and glucose through GT, CDT, ST, and chemotherapeutic mechanisms. Therefore, the designing of CuCGC nanocatalysts by coupling ROS-generator with stimuli-responsive drug was potential candidates in clinical studies.