Liver fibrosis is a wound healing process marked by excessive accumulation of extracellular matrix in the liver. A poly(rC)‐binding protein 2 (PCBP2) siRNA that reverses fibrogenesis in activated hepatic stellate cells (HSCs) has been recently discovered. However, targeted delivery of siRNAs to HSCs still remains a daunting challenge. Herein, a new strategy is developed to fabricate a multicomponent nanocomplex using siRNA/peptide nucleic acid (PNA) hybrid instead of chemically conjugated siRNA, thus increasing the scalability and feasibility of the siRNA nanocomplex for animal studies. The nanocomplex is modified with an insulin growth factor 2 receptor ‐specific peptide, which specifically binds to activated HSCs. The siRNA nanocomplex demonstrates a controllable size, high serum stability, and high cellular uptake in activated HSCs in vitro and in vivo. Anti‐fibrotic activity of the siRNA nanocomplex is evaluated in rats with carbon tetrachloride‐induced liver fibrosis. Treatment with the PCBP2 siRNA nanocomplex significantly inhibits the mRNA expressions of PCBP2 and type I collagen in fibrotic liver. The histology study reveals that the siRNA nanocomplex efficiently reduces the protein level of type I collagen and reverses liver fibrosis. The data suggests that the nanocomplex efficiently delivers the siRNA to fibrotic liver and produces a potent anti‐fibrotic effect.
- Award ID(s):
- 2145491
- PAR ID:
- 10436329
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 14
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41467-022-35637-z
