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• W4372203603 endingPage "122134" @default.
• W4372203603 startingPage "122134" @default.
• W4372203603 abstract "Activated hepatic stellate cell (aHSC) is mainly responsible for deposition of extracellular collagen matrix that causes liver fibrosis. Although several siRNAs adequately inhibited HSC activation in vitro, they were demonstrated poor RNAi efficiency in vivo. Developing HSC-targeting and cytoplasmic delivery nanocarrier is highly essential to acquire a desirable siRNA therapeutic index for anti-liver fibrosis. Here, we developed a unique crosslinking nanopolyplex (called T-C-siRNA) modified by vitamin A (VA) with the well-designed natures, including the negative charge, retinol-binding protein (RBP) hijacking, and cytoplasmic siRNA release in response to ROS and cis diol molecules. The nanopolyplex was given a yolk-shell-like shape, camouflage ability in blood, and HSC-targeting capability by hijacking the endogenous ligand RBP via surface VA. PDGFR-β siRNA (siPDGFR-β) supplied via T-C-siPDGFR-β nanopolyplex dramatically reduced HSC activation and its production of pro-fibrogenic proteins in vitro and in vivo. Furthermore, T-C-siPDGFR-β nanopolyplex effectively alleviated CCl4-induced liver injury, decreased hepatic collagen sediment, and recovered liver function in mice. This study provides a sophisticated method for HSC-targeting cytoplasmic RNA delivery using endogenous ligand hijacking and dual sensitivity of ROS and cis diol compounds." @default.
• W4372203603 created "2023-05-07" @default.
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• W4372203603 date "2023-08-01" @default.
• W4372203603 modified "2023-10-14" @default.
• W4372203603 title "Retinol-binding protein-hijacking nanopolyplex delivering siRNA to cytoplasm of hepatic stellate cell for liver fibrosis alleviation" @default.
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• W4372203603 doi "https://doi.org/10.1016/j.biomaterials.2023.122134" @default.
• W4372203603 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37167895" @default.
• W4372203603 hasPublicationYear "2023" @default.
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