Journal
JOURNAL OF NANOBIOTECHNOLOGY
Volume 18, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12951-020-00645-y
Keywords
Hepatic stellate cells; Germacrone; miR-29b; cRGDfK; Liver fibrosis therapy
Funding
- National Key RAMP
- D Program of China [2018YFC1707000]
- National Natural Science Foundation of China [81973483, 81673598, 81473349]
- Natural Science Foundation of the Jiangsu Higher Education Institutions of China [18KJB360008]
- National Standardization Program for Chinese Medicine [ZYBZH-Y-SC-40]
- Special Fund for Research in the public interest [201507002-2]
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Hepatic stellate cells (HSCs) were activated and secreted excessive amounts of extracellular matrix (ECM) proteins during pathogenetic progress of liver fibrosis. Germacrone (GMO) and miR-29b can play an important role in inhibiting growth of HSCs and production of type I collagen. GMO and miR-29b were co-encapsulated into nanoparticles (NPs) based on poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA). Then, NPs were modified with cyclic RGD peptides (cRGDfK). cRGDfK is an effective ligand to bind integrin alpha(v)beta(3) and increase the targeting ability for fibrotic liver. GMO- and miR-29b-loaded NPs exhibited great cytotoxicity to activated HSCs and significantly inhibited production of type I collagen. Liver fibrosis model of mice was induced by administration of carbon tetrachloride. Great targeting ability was achieved in liver fibrotic mice treated with cRGD-modified NPs. Significant ant-fibrotic effects have been presented based on hematoxylin and eosin (H&E), Masson and Sirius Red staining results of liver tissues collected from mice treated with drug-loaded NPs. All these results indicate GMO- and miR-29b-loaded cRGD-modified NPs have the potential for clinical use to treat liver fibrosis.
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