A Polymer Multicellular Nanoengager for Synergistic NIR-II Photothermal Immunotherapy.

Cell-membrane-coated nanoparticles (CCNPs) that integrate the biophysiological advantages of cell membranes with the multifunctionalities of synthetic materials hold great promise in cancer immunotherapy. However, strategies have yet to be revealed to further improve their immunotherapeutic efficacy. Herein, a polymer multicellular nanoengager (SPNE) for synergistic second-near-infrared-window (NIR-II) photothermal immunotherapy is reported. The nanoengager consists of an NIR-II absorbing polymer as the photothermal core, which is camouflaged with fused membranes derived from immunologically engineered tumor cells and dendritic cells (DCs) as the cancer vaccine shell. In association with the high accumulation in lymph nodes and tumors, the multicellular engagement ability of the SPNE enables effective cross-interactions among tumor cells, DCs, and T cells, leading to augmented T cell activation relative to bare or tumor-cell-coated nanoparticles. Upon deep-tissue penetrating NIR-II photoirradiation, SPNE eradicates the tumor and induces immunogenic cell death, further eliciting anti-tumor T cell immunity. Such a synergistic photothermal immunotherapeutic effect eventually inhibits tumor growth, prevents metastasis and procures immunological memory. Thus, this study presents a general cell-membrane-coating approach to develop photo-immunotherapeutic agents for cancer therapy.