Thermoresponsive and Substrate Self-Cycling Nanoenzyme System for Efficient Tumor Therapy

Cerium oxide (CeO_2-) performs well in photothermal and catalytic properties due to its abundance of oxygen vacancies. Based on this, we designed a thermosensitive therapeutic nanoplatform to achieve continuous circular drug release in tumor. It can solve the limitation caused by insufficient substrate in the process of tumor treatment. Briefly, CeO_2- and camptothecin (CPT) were wrapped in an agarose hydrogel, which could be melted by the photothermal effect of CeO_2-. At the same time, the local temperature increase provided photothermal treatment, which could induce the apoptosis of tumor cell. After that, CPT was released to damage the DNA in tumor cells to realize chemical treatment. In addition, CPT could active nicotinamide adenine dinucleotide oxidase to react with O₂ to increase the intracellular H₂O₂. After that, the exposed CeO_2- could catalyze H₂O₂ to generate cytotoxic reactive oxygen species for chemodynamic therapy. More importantly, CeO_2- could catalyze H₂O₂ to produce O₂, which could combine with the catalytic action of CPT to construct a substrate self-cycling nanoenzyme system. Overall, this self-cycling nanoplatform released hypoxia in the tumor microenvironment and built a multimode tumor treatment, which achieved an ideal antitumor affect.