Polymer‐Reinforced Liposomes Amplify Immunogenic Cell Death‐Associated Antitumor Immunity for Photodynamic‐Immunotherapy

Abstract Photodynamic therapy has emerged as a promising tool for inducing immunogenic cell death (ICD), which shows the potential to convert tumor cells into in situ vaccines. However, large amounts of as‐generated tumor‐associated antigens (TAAs) are entrapped in the endo‐lysosomes of tumor‐infiltrating dendritic cells (DCs), resulting in unsatisfactory TAA cross‐presentation and poor or moderate ICD‐associated antitumor responses. Herein, an immune‐enhancing polymer‐reinforced liposome (IERL) with a stable nanostructure and a bioactive surface is developed and it demonstrates its capability to collect TAAs, facilitates TAA endo‐lysosomal escape in DCs, and enhances cross‐presentation of TAAs, which results in the amplification of ICD‐associated antitumor immune responses. By loading photosensitizers, IERLs are able to induce robust antitumor immune responses and immune memory after local irradiation, thereby inhibiting the growth of both primary and distant/metastatic tumors. Additionally, considering the wide applications of liposomal carriers, photosensitizers in IERLs can be easily replaced with photothermal agents and radiosensitizers (or their combinations), which provides a general platform for the rapid development of combined cancer immunotherapy.