Photothermal nanobomb blocking metabolic adenosine-A2AR potentiates infiltration and activity of T cells for robust antitumor immunotherapy

An immunostimulant black phosphorus nanobomb Apt@SCH@BPs is developed. By synergism of photothermia and adenosine-A2AR blockade, Apt@SCH@BPs can attenuate tumor stroma, promote DCs maturation, inhibit Tregs activity, and further enhance the filtration and cytotoxicity of T cells, boosting robust antitumor immunity and suppressing tumor growth efficiently. [Display omitted] •A novel photothermal A2AR-blocking black phosphorus nanobomb is developed.•The nanobomb attenuates tumor stroma, potentiating infiltration of T cells.•The nanobomb promotes activity of T cells, boosting robust antitumor immunity.•A2AR-blocking based photoimmunotherapy suppresses tumor growth efficiently. Immunotherapy has partly achieved striking outcomes in the clinic for specific tumors. However, the responses are still limited for tumors that have restricted filtration and decreased activity of cytotoxic T cells due to the tumor stroma physical obstacles and immune-suppressive factors. Here we report an effective synergistic strategy for tumor therapy via integrating photothermal therapy and blockade of metabolic immune pathway adenosine based on a novel black phosphorus nanobomb. By rational conjugation of adenosine A2A receptor inhibitor SCH442416 (SCH) and targeting aptamer AS1411 (Apt) on black phosphorus nanosheets (BPs), we fabricate an immunostimulant nanobomb Apt@SCH@BPs. Apt@SCH@BPs shows good targeting and accumulation in melanoma. By synergism of photothermia and adenosine blockade, Apt@SCH@BPs could not only directly ablate tumor cells, but also boost maturation of dendritic cells, inhibit the regulatory T cells, stimulate the cytotoxic T cells, and elicit their filtration by attenuating tumor stromal barriers (e. g., cancer-associated fibroblasts and collagen). This synergistical therapy efficiently suppresses the growth of melanoma, and might be potential for other solid tumors.