Autophagy‐Inducing MoO3‐x Nanowires Boost Photothermal‐Triggered Cancer Immunotherapy

Abstract Autophagy could play suppressing role in cancer therapy by facilitating release of tumor antigens from dying cells and inducing immunogenic cell death (ICD). Therefore, discovery and rational design of more effective inducers of cytotoxic autophagy is expected to develop new strategies for finding innovative drugs for precise and successful cancer treatment. Herein, we develop MoO 3‐x nanowires (MoO 3‐x NWs) with high oxygen vacancy and strong photothermal responsivity to ablate tumors through hyperthermia, thus promote the induction of cytotoxic autophagy and severe ICD. As expected, the combination of MoO 3‐x NWs and photothermal therapy (PTT) effectively induces autophagy to promote the release of tumor antigens from the ablated cells, and induces the maturation and antigen presentation of dendritic cells (DCs), subsequently activates cytotoxic T lymphocytes (CTLs)‐mediated adaptive immunity. Furthermore, the combination treatment of MoO 3‐x NWs with immune checkpoint blockade of PD‐1 could promote the tumor‐associated macrophages (TAMs) polarization into tumor‐killing M1 macrophages, inhibit infiltration of Treg cells at tumor sites, and alleviate immunosuppression in the tumor microenvironment, finally intensify the anti‐tumor activity in vivo. This study provides a strategy and preliminary elucidation of the mechanism of using MoO 3‐x nanowires with high oxygen vacancy to induce autophagy and thus enhance photothermal immunotherapy.