Tumor Microenvironment‐Responsive Nanocarrier Based on VOx Nanozyme Amplify Oxidative Stress for Tumor Therapy

Abstract The construction of a novel nanocarrier that can break the redox balance in tumor cell is a promising anti‐tumor strategy. Herein, a tumor microenvironment (TME)‐responsive nanocarrier VC@Lipo is rationally designed by embedding ultrasmall VO x nanozyme and photosensitizer chlorin e6 (Ce6) into liposomes. The size of VC@Lipo nanocarrier is ≈35 nm and can be degraded in the weakly acidic environment of TME. The VO x nanozyme exhibits peroxidase‐like activity and generates highly toxic hydroxyl radical ∙OH through Fenton‐like reaction and 1 O 2 in the presence of H 2 O 2 independent of light, and more 1 O 2 can be generated by the photodynamic effect of Ce6. In addition, the VO x nanozyme can effectively deplete intracellular overexpressed glutathione (GSH) through redox reactions. In vivo experiments demonstrate that the nanocarrier shows excellent biocompatibility, presents the largest enrichment at the tumor site after 6 h of intravenous injection into mice with the highest tumor inhibition rate of 54.18% after laser irradiation. Compared with the single treatment mode, VC@Lipo shows the best synergistic effect of chemodynamic‐photodynamic therapy. This work provides a new paradigm for nanocatalytic therapy of cancer and is expected to provide new ideas for precision medicine in cancer.