2. Academic Validation
  3. Integrin β4-Enriched Small Extracellular Vesicle as Drug Delivery Vehicle for Targeting Pulmonary Metastasis of Hepatocellular Carcinoma

Integrin β4-Enriched Small Extracellular Vesicle as Drug Delivery Vehicle for Targeting Pulmonary Metastasis of Hepatocellular Carcinoma

  • Adv Healthc Mater. 2025 Jul 14:e2502649. doi: 10.1002/adhm.202502649.
Tung Him Ng 1,  Aijun Liang 1 2,  Maximus Cf Yeung 1,  Sze Keong Tey 3,  Kam-Leung Siu 4,  Sin-Yee Fung 4,  Dong-Yan Jin 4,  Judy Wai Ping Yam 1 2 5 6
Affiliations

Affiliations

  • 1 Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 510282, P. R. China.
  • 2 Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, P. R. China.
  • 3 Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, P. R. China.
  • 4 School of Biomedical Sciences, The University of Hong Kong, 21 Sassoon Road,Pokfulam, Hong Kong, P. R. China.
  • 5 State Key Laboratory of Liver Research (The University of Hong Kong), Hong Kong, P. R. China.
  • 6 Materials Innovation Institute for Life Sciences and Energy (MILES), HKU-SIRI, Shenzhen, 518057, P. R. China.
PMID: 40653907 DOI: 10.1002/adhm.202502649
Abstract

Small extracellular vesicles (sEVs) hold significant promise for targeted drug delivery, owing to their unique ability to target and accumulate in specific tissues. The organotropism of sEVs is primarily determined by the presence of integrins on their surface. In this study, sEV with enriched Integrin β4, designated as XP-ITGβ4-sEV, are engineered to enhance lung-targeting capabilities. The therapeutic efficacy of doxorubicin-loaded XP-ITGβ4-sEV (XP-ITGβ4-sEV/Dox) is evaluated in targeting pulmonary metastasis of advanced hepatocellular carcinoma (HCC) using a murine lung metastasis model. Remarkably, treatment with XP-ITGβ4-sEV/Dox effectively suppresses tumor cell colonization in the lungs compared to an equivalent dose of free doxorubicin. Histological analyses reveal a reduction in lung metastatic foci, inhibition of proliferation, and an increase in Apoptosis of HCC cells. Notably, XP-ITGβ4-sEV/Dox exhibits a superior therapeutic efficacy with an improved safety profile compared to a higher dose of free doxorubicin that demonstrates similar efficacy. These findings collectively underscore the potential of Integrin β4-enriched sEVs as a targeted drug delivery system for addressing pulmonary metastasis of HCC.

Keywords

drug deliveries; extracellular vesicles; hepatocellular carcinoma; integrins; lung metastases.

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