Erythrocyte-inspired biomaterials for cancer immunotherapy: Integration within the cancer-immunity cycle.

Abstract

Erythrocyte-based drug delivery systems serve as an attractive strategy for cancer immunotherapy with improved biocompatibility, increased circulation time, and less immunogenicity. Due to their distinct physiological characteristics, erythrocytes can be developed as biomimetic carriers for targeted drug delivery, antigen presentation, and immune modulation. This review discusses the different strategies utilized to leverage erythrocytes in cancer immunotherapy, such as erythrocyte membrane-coated nanoparticles, antigen-hitchhiking systems, and immune-stimulatory erythrocyte-derived vesicles. Notably, we uniquely contextualizes erythrocyte-inspired platforms across each stage of the cancer-immunity cycle, highlighting their dual role as both drug delivery vehicles and active immunomodulators. We have explained how engineered erythrocyte-based systems enhance the cycle of cancer-immunity by increasing tumor antigen presentation and reshaping the tumor microenvironment for greater immune cell infiltration and cytotoxicity. In addition, recent advances in erythrocyte-based immunotherapeutic platforms, their advantages over conventional delivery platforms, and challenges in their clinical application are discussed. Overall, the integration of erythrocyte biomimetic technology into immunotherapy provides a novel approach to enhance cancer treatment efficacy and reduce systemic toxicity, paving the way for more targeted and effective therapies.