Abstract
Low density lipoprotein (LDL) plays an important role in transporting fat molecules including cholesterols in the body. In this work, cationic solid lipid nanoparticles (CSLNs), bioinspired and reconstituted from natural LDLs, were designed and applied to target specific systemic delivery of connective tissue growth factor siRNA (siCTGF) for the treatment of liver fibrosis. They could form a nuclease-resistant stable nano-complex with siRNA, which was efficiently internalized into cells achieving targeted gene silencing in the presence of serum with a remarkably low cytotoxicity. After intravenous injection, CSLN/siCTGF complex was target specifically delivered to the liver and resulted in a significant reduction in collagen content and pro-fibrogenic factors like tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), interleukin-6 (IL-6), and CTGF with the dramatic improvement of patho-physiological symptoms in liver fibrosis model rats. The bio-distribution study by fluorescence bioimaging and single-photon emission computed tomography (SPECT) confirmed the target specific delivery and accumulation of CSLN/siCTGF complexes to the liver tissues.
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