Fibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis

Jaiwoo Lee, Junho Byun, Gayong Shim and Yu-Kyoung Oh ()
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Jaiwoo Lee: Seoul National University
Junho Byun: Seoul National University
Gayong Shim: Soongsil University
Yu-Kyoung Oh: Seoul National University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract In liver fibrosis, activated hepatic stellate cells are known to overexpress fibroblast activation protein. Here we report a targeted antifibrotic peptide-delivery system in which fibroblast activation protein, which is overexpressed in fibrotic regions of the liver, liberates the antifibrotic peptide melittin by cleaving a fibroblast activation protein-specific site in the peptide. The promelittin peptide is linked to pegylated and maleimide-functionalized liposomes, resulting in promelittin-modified liposomes. The promelittin-modified liposomes were effective in reducing the viability of activated hepatic stellate cells but not that of control cells. In three types of liver fibrosis mouse models, intravenously administered promelittin-modified liposomes significantly reduces fibrotic regions. In addition, in the bile duct ligation mouse model promelittin-modified liposome-treatment increases overall survival. Although this peptide-delivery concept was tested for liver fibrosis, it can potentially be adapted to other fibrotic diseases.

Date: 2022
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DOI: 10.1038/s41467-022-29186-8

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