Stapled Liposomes Enhance Cross-priming of Radio-immunotherapy.

The release of tumor-associated antigens (TAAs) and their cross-presentation in dendritic cells (DCs) are crucial for radio-immunotherapy. However, the irradiation resistance of tumor cells usually results in limited TAA generation and release. Importantly, TAAs internalized by DCs are easily degraded in lysosomes, resulting in unsatisfactory extent of TAA cross-presentation. Herein, we developed an antigen-capturing stapled liposome (ACSL) with a robust structure and bioactive surface. The ACSLs captured and transported TAAs from lysosomes to the cytoplasm in DCs, thereby enhancing TAA cross-presentation. L-arginine encapsulated in ACSLs induced robust T cell-dependent antitumor response and immune memory in 4T1 tumor-bearing mice after local irradiation, resulting in significant tumor suppression and an abscopal effect. Replacing L-arginine with radiosensitizers, photosensitizers, and photothermal agents may make ACSL a universal platform for the rapid development of various combinations of anticancer therapies. This article is protected by copyright. All rights reserved.