<i>In vitro</i>, the HCS-LGP NPs showed efficient cellular uptake in TGF-β1-induced HK-2 cells and significantly inhibited cell proliferation by downregulating the expression of TGF-β1 and Collagen I. <i>In vivo</i> studies demonstrated effective renal accumulation of HCS-LGP NPs in rats with renal fibrosis. The gene discussed is TGFB1; the disease is renal fibrosis.