Tumor Microenvironment‐Responsive Nanocarrier Based on VO_x 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 ¹O₂ in the presence of H₂O₂ independent of light, and more ¹O₂ 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.