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

Tung Him Ng1, Aijun Liang1,2, Maximus Cf Yeung1

  • 1Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 510282, P. R. China.

Advanced Healthcare Materials
|July 14, 2025
PubMed

Insights

Engineered small extracellular vesicles (sEVs) enriched with integrin β4 show promise for lung cancer treatment. These XP-ITGβ4-sEVs loaded with doxorubicin effectively target pulmonary metastasis with improved safety.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Small extracellular vesicles (sEVs) are promising for targeted drug delivery due to inherent tissue-specific accumulation.
  • Integrins on sEV surfaces dictate their organotropism, influencing biodistribution and targeting efficiency.

Purpose of the Study:

  • To engineer sEVs enriched with integrin β4 (XP-ITGβ4-sEV) to enhance lung-targeting capabilities.
  • To evaluate the therapeutic efficacy of doxorubicin-loaded XP-ITGβ4-sEV (XP-ITGβ4-sEV/Dox) against pulmonary metastasis of hepatocellular carcinoma (HCC).

Main Methods:

  • Engineering of sEVs with enriched integrin β4.
  • Loading of doxorubicin into engineered sEVs.
  • Evaluation in a murine lung metastasis model of HCC.
  • Histological analysis of lung tissue, tumor cell proliferation, and apoptosis.

Main Results:

  • XP-ITGβ4-sEV/Dox significantly suppressed lung tumor cell colonization compared to free doxorubicin.
  • Histological analysis showed reduced lung metastatic foci, inhibited proliferation, and increased apoptosis.
  • XP-ITGβ4-sEV/Dox demonstrated superior therapeutic efficacy and an improved safety profile.

Conclusions:

  • Integrin β4-enriched sEVs represent a viable strategy for targeted delivery of chemotherapy to lung metastases.
  • XP-ITGβ4-sEV/Dox holds potential for treating pulmonary metastasis in advanced HCC.
  • This approach offers enhanced efficacy and safety compared to conventional doxorubicin administration.
Keywords:
drug deliveriesextracellular vesicleshepatocellular carcinomaintegrinslung metastases

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