A combined "eat me/don't eat me" strategy based on exosome for acute liver injury treatment.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-03-14 DOI:10.1016/j.xcrm.2025.102033

Wei Du, Chen Chen, YingYing Liu, Huiyi Quan, Ming Xu, JingJing Liu, Ping Song, ZhiQiang Fang, ZhenSheng Yue, Hao Xu, YuWei Ling, JuanLi Duan, Fei He, Lin Wang

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引用次数: 0

Abstract

Drug-induced liver injury (DILI) involves multifaceted pathogenesis, necessitating effective therapeutic strategies. Wnt2, secreted by liver sinusoidal endothelial cell (LSEC), activates the Wnt/β-catenin signaling pathway to promote hepatocyte proliferation after injury. To address the dual challenges of targeted delivery and phagocytosis evasion, we develop a combined "eat me/don't eat me" strategy. RLTRKRGLK (RLTR) peptide-functionalized exosomes are engineered by inserting DMPE-PEG2000-CRLTRKRGLK into the lipid membrane of exosome derived from bEnd.3 cell. Surface-displayed RLTR mediates exosomal enrichment in LSEC, while CD47 engineering reduces macrophage clearance via "don't eat me" signaling. Then, lentiviral transfection enables stable encapsulation of functional Wnt2 mRNA into Exo^CD47 (designated Wnt2@Exo^CD47). In both acetaminophen (APAP) and dimethylnitrosamine (DMN)-induced murine liver injury models, RLTR-Wnt2@Exo^CD47 demonstrates LSEC-specific targeting and significant hepatoprotection. This engineered exosome platform provides a therapeutic strategy for DILI.

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.