Biomimetic Layered Molybdenum Oxide Nanosheets with Excellent Photothermal Property Combined with Chemotherapy for Enhancing Anti-Tumor Immunity

The development and application of two-dimensional nanomaterials with imaging, drug carrier, and photothermal therapy (PTT) functions have bright prospects in the biomedical field. However, the strong hydrophobicity and difficult degradation of most two-dimensional materials limit their in vivo application. Here, a bionic nanoplatform MoOx@M-SN38 with high photothermal absorption and good biodegradability based on molybdenum oxide nanosheet was prepared. Phospholipid modification and coated with 4T1 tumor cell membrane endowed strongly hydrophobic nanosheet with good dispersibility and stability in the aqueous medium and effective accumulation at the tumor site after intravenous injection. The loaded 7-ethyl-10-hydroxycamptothecin (SN38), a topoisomerase I inhibitor, could not only induce immunogenic cell death (ICD) and play a synergistic role with ICD produced by photothermic agent, but also induce the production of type I interferon and the activation of STING pathway, jointly promoting the maturation of dendritic cells and alleviating the immunosuppressive environment of tumors. The in vivo experiment results indicated that MoOx@M-SN38 nanosheets could effectively inhibit the primary tumor and lung metastasis compared with monotherapy. The novel MoOx@M-SN38 nanosheets could achieve the combination of PTT and chemotherapy and significantly enhance the anti-tumor immunity, and are expected to become a multifunctional and promising platform for nanomedicine applications.