A Defect-Engineered Nanozyme for Targeted NIR-II Photothermal Immunotherapy of Cancer

Multienzyme-mimicking redox nanozymes, curated by defect engineering, in synergy with immunotherapy offer promising prospects for safe and efficient cancer therapy. However, the spatiotemporally precise immune response often gets challenged by off-target adverse effects and insufficient therapeutic response. Herein, a tumor cell membrane coated redox nanozyme (CMO-R@4T1) is reported for combinational second near-infrared window (NIR-II) photothermal immunotherapy. CMO-R@4T1 consists of a Cu-doped MoO_x (CMO) nanozyme as the core, which is cloaked with tumor-cell-derived fused membranes with immunostimulants immobilized in the membrane shell. In addition to the enhanced tumor accumulation, the nanozyme can cause oxidative damage to tumor cells by the production of reactive oxygen species and attenuation of the antioxidant mechanism. CMO-R@4T1 also mediates a photothermal effect under NIR-II photoirradiation to trigger tumor eradication and immunogenic cell death, where the liberated agonist elicits the immune activation. Such a controlled therapeutic paradigm potentiates systemic primary tumor ablation, inhibits cancer metastasis to distant tumor, and procures long-term immunological memory. Thereby, this study takes advantage of defect engineering to illustrate a generic strategy to prepare cell-membrane-camouflaged nanozymes for targeted photo-immunotherapy of cancer.