Fused Cytomembrane‐Camouflaged Nanoparticles for Tumor‐Specific Immunotherapy

Abstract Tumor immunotherapy is commonly hindered by inefficient delivery and presentation of tumor antigens as well as immunosuppressive tumor microenvironment. To overcome these barriers, a tumor‐specific nanovaccine capable of delivering tumor antigens and adjuvants to antigen‐presenting cells and modulating the immune microenvironment to elicit strong antitumor immunity is reported. This nanovaccine, named FCM@4RM, is designed by coating the nanocore (FCM) with a bioreconstituted cytomembrane (4RM). The 4RM, which is derived from fused cells of tumorous 4T1 cells and RAW264.7 macrophages, enables effective antigen presentation and stimulation of effector T cells. FCM is self‐assembled from Fe(II), unmethylated cytosine‐phosphate‐guanine oligodeoxynucleotide (CpG), and metformin (MET). CpG, as the stimulator of toll‐like receptor 9, induces the production of pro‐inflammatory cytokine and the maturation of cytotoxic T lymphocytes (CTLs), thereby enhancing antitumor immunity. Meanwhile, MET functions as the programmed cell death ligand 1 inhibitor and can restore the immune responses of T cells against tumor cells. Therefore, FCM@4RM exhibits high targeting capabilities toward homologous tumors that develop from 4T1 cells. This work offers a paradigm for developing a nanovaccine that systematically regulates multiple immune‐related processes to achieve optimal antitumor immunotherapy.