Physiologically triggered injectable red blood cell-based gel for tumor photoablation and enhanced cancer immunotherapy

Abstract

Hydrogels are widely used for drug delivery and tissue engineering. Here we developed a simple injectable red blood cells (RBCs)-based gel for cancer photo-immunotherapy. We find that subcutaneous injected homologous RBCs could form hydrogel-like composition in mice, due to the infiltrated platelets and thrombin under physiological environment. In addition, the formed RBC-gel has photothermal effect under NIR laser exposure on account of deep reddish color. In mice bearing CT26 tumors, we demonstrate photo-immunotherapy of cancer by local injection of imiquimod (R837) adjuvant engineered RBCs. The photothermal effect of the in situ formed RBC-gel effectively burns tumor to release tumor-associated antigens (TAAs), promotes the release of R837 from RBCs to the tumor draining lymph node, thereby activating the lymph node-resident antigen-presenting cells (APCs) remarkably. A durable systemic immune response is induced following the combination treatment of the primary tumor. 100% mice rejected tumor rechallenge and are survived at least 250 days without any detectable tumors. Our strategy highlights the RBCs, the most common type of cell in our blood, as the hydrogel for drug delivery and cancer photo-immunotherapy.