{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T06:17:56Z","timestamp":1775110676117,"version":"3.50.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373183"],"award-info":[{"award-number":["82373183"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CAR-T therapy is limited by off-target sequestration in liver, spleen, and lungs, which reduces tumor delivery and risks systemic toxicity. Genetic engineering approaches are complex and carry safety concerns, necessitating efficient non-genetic strategies to optimize CAR-T biodistribution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We developed red blood cell membrane\u2013chimeric liposomes (Rlip) as a biomimetic coating system to non-genetically modify CAR-T cells, aiming to enhance immune evasion, prolong circulatory persistence, and redirect trafficking toward tumors while preserving intrinsic effector function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Rlip-CAR-T cells were prepared via simple incubation.\n                      <jats:italic>In vitro<\/jats:italic>\n                      characterization assessed coating stability, CD47-mediated macrophage resistance, phenotype preservation, and antigen-specific cytotoxicity.\n                      <jats:italic>In vivo<\/jats:italic>\n                      studies evaluated biodistribution, tumor infiltration, and efficacy in Nalm-6 systemic leukemia and 1806-luc subcutaneous ovarian cancer models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Rlip coating stably presented CD47, functionally impairing macrophage phagocytosis and enhancing peripheral persistence without altering memory subsets, activation markers, or cytotoxicity. Rlip-CAR-T cells demonstrated markedly reduced off-target organ accumulation and increased intratumoral enrichment in both models, with superior tumor control and prolonged survival observed in the leukemia model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Rlip surface engineering represents a universal, clinically translatable strategy to overcome CAR-T biodistribution barriers. By integrating erythrocyte-mimetic immune evasion with optimized tumor delivery, this approach improves CAR-T cell accumulation at tumor sites across hematologic and solid malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1799107","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:23:45Z","timestamp":1775107425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Erythrocyte membrane\u2013liposome coating sustains circulation stability and targeted tumor therapy of CAR-T cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiying","family":"Chen","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University","place":["Nanjing, 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