Artificial Nanoscale Erythrocytes from Clinically Relevant Compounds for Enhancing Cancer Immunotherapy

Because of enhanced efficacy and lower side effects, cancer immunotherapies have recently been extensively investigated in clinical trials to overcome the limitations of conventional cancer monotherapies. Although engineering attempts have been made to build nanosystems even including stimulus nanomaterials for the efficient delivery of antigens, adjuvants, or anticancer drugs to improve immunogenic cancer cell death, this requires huge R&D efforts and investment for clinically relevant findings to be approved for translation of the nanosystems. To this end, in this study, an air–liquid two-phase electrospray was developed for stable bubble pressing under a balance between mechanical and electrical parameters of the spray to continuously produce biomimetic nanosystems consisting of only clinically relevant compounds [paclitaxel-loaded fake blood cell Eudragit particle (Eu-FBCP/PTX)] to provide a conceptual leap for the timely development of translatable chemo-immunotherapeutic nanosystems. This was pursued as the efficacy of systems for delivering anticancer agents that has been mainly influenced by nanosystem shape because of its relevance to transporting behavior to organs, blood circulation, and cell–membrane interactions. The resulting Eu-FBCP/PTX nanosystems exhibiting phagocytic and micropinocytic uptake behaviors can confer better efficacy in chemo-immunotherapeutics in the absence and presence of anti-PD-L1 antibodies than similar sized PTX-loaded spherical Eu particles (Eu-s/PTX). [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40820-020-00428-y) contains supplementary material, which is available to authorized users.