Combinatorial Neoadjuvant and Photoinduced Adoptive Cellular Immunotherapy via MXene Nanosphere

Adoptive T-cell therapy is a modest technique to trigger therapeutic T-cells, but the tumor desmoplastic structure and its immunosuppressive microenvironment account for the reduced efficacy of T-cells. NIR-based phototherapy is a promising modality which is able to trigger the T-cells by a photothermal effect. In certain cases, NIR irradiation affecting the neighboring tissue remains a significant challenge. Taking inspiration from MXene can induce mild heat to initiate the immunomodulatory effect. It controls the heat, limits heat transfer, and makes tumors more receptive to immune checkpoint inhibitors. Here, we provided a combinatorial adoptive T-cell therapy (ATCT) approach through the photothermal effect of MXene nanosheet-coated silica nanoparticles (MX/SiNPs) and delivery of immunoadjuvant (BCG) and (TLR 7/8a). MX/SiNPs exhibited 78% and 76% release of BCG and TLR 7/8a, respectively, at pH 5.0. Upon exposure to bone marrow-derived dendritic cells (BMDCs), MX/SiNPs actively penetrated the cells; the photothermal effect generated heat up to 43 °C which impacted the cell viability. Effective release of immunoadjuvant leads to maturation of BMDCs, and mild heat readily activates the T-cells. It can be evidenced that 50 μg/mL treatment measures the secretion of TNF-α, IL-6, 12p70, and 1β. In vivo, the photothermal effect induced dendritic cell (DCs) activation of T-cells, which shows greater tumor regression. NIR-activated T-cells increase the IFN-γ and IL-2 inflammatory cytokines, and CD8+ and CD4+ T-cell levels. Our findings demonstrate the neoadjuvant and photothermal effect of MX/SiNPs, which can be used as an effective and safe platform for targeted adoptive cellular cancer immunotherapy.