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

摘要

Photodynamic therapy has emerged as a promising tool for inducingimmunogenic cell death (ICD), which shows the potential to converttumor cells into in situ vaccines. However, large amounts of as-generatedtumor-associated antigens (TAAs) are entrapped in the endo-lysosomes oftumor-infiltrating dendritic cells (DCs), resulting in unsatisfactory TAA crosspresentationand poor or moderate ICD-associated antitumor responses.Herein, an immune-enhancing polymer-reinforced liposome (IERL) with astable nanostructure and a bioactive surface is developed and it demonstratesits capability to collect TAAs, facilitates TAA endo-lysosomal escape in DCs,and enhances cross-presentation of TAAs, which results in the amplificationof ICD-associated antitumor immune responses. By loading photosensitizers,IERLs are able to induce robust antitumor immune responses and immunememory after local irradiation, thereby inhibiting the growth of both primaryand distant/metastatic tumors. Additionally, considering the wide applicationsof liposomal carriers, photosensitizers in IERLs can be easily replacedwith photothermal agents and radiosensitizers (or their combinations), whichprovides a general platform for the rapid development of combined cancerimmunotherapy.