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

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

  • Cell Rep Med. 2025 Mar 14:102033. doi: 10.1016/j.xcrm.2025.102033.
Wei Du 1,  Chen Chen 1,  YingYing Liu 1,  Huiyi Quan 2,  Ming Xu 1,  JingJing Liu 1,  Ping Song 1,  ZhiQiang Fang 1,  ZhenSheng Yue 1,  Hao Xu 1,  YuWei Ling 1,  JuanLi Duan 3,  Fei He 4,  Lin Wang 5
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
  • 2 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
  • 3 Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: duan_juan_li@126.com.
  • 4 Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: hefei_hefei@163.com.
  • 5 Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: fierywang@163.com.
PMID: 40120577 DOI: 10.1016/j.xcrm.2025.102033
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 ExoCD47 (designated Wnt2@ExoCD47). In both acetaminophen (APAP) and dimethylnitrosamine (DMN)-induced murine liver injury models, RLTR-Wnt2@ExoCD47 demonstrates LSEC-specific targeting and significant hepatoprotection. This engineered exosome platform provides a therapeutic strategy for DILI.

Keywords

Wnt/β-catenin pathway; drug-induced liver injury; engineered exosome; liver regeneration; liver sinusoidal endothelial cell.

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