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  • Title: Facile Fabrication of Nanoparticles with Dual-Targeting Ligands for Precise Hepatocellular Carcinoma Therapy In Vitro and In Vivo.
    Author: Xiang Y, Huang W, Huang C, Long J, Zhou Y, Liu Y, Tang S, He DX, Tan XW, Wei H, Yu CY.
    Journal: Mol Pharm; 2020 Sep 08; 17(9):3223-3235. PubMed ID: 32658485.
    Abstract:
    Efficient hepatocellular carcinoma (HCC) therapy remains a significant challenge due to the unsatisfactory targeting efficiency of nanoparticles (NPs) with either a passive targeting or a single active targeting property. Although a dual-targeting mechanism-based strategy can promote the partial targeting efficiency, most of the reported NPs with dual-targeting properties generally suffer from sophisticated chemical design, multistep synthesis, and purification procedures, leading to batch-to-batch variation and difficulties in scalable production. To develop a facile yet efficient strategy toward dual-targeting ligand-functionalized NPs for precise HCC therapy and potential clinical translation, folic acid (FA) was readily introduced as a hydrophobic and targeting component to a hydrophilic macromolecular prodrug, galactosylated chitosan-5-fluorouracil acetic acid (GC-FU), to afford FA-GC-FU formulation that can self-assemble into NPs driven by the solubility variation of FA and GC-FU without the necessity of previously used physical cross-linking. The resulting nanoparticles of FA-GC-FU can target the overexpressed asialoglycoprotein receptors (ASGPRs) and folate receptors (FRs) on the surface of HCC cells, respectively, via the FA and lactobionic acid (LA) residues exposed on the surface of the NPs, leading to the maximized targeting efficiency of HCC and minimized nonspecific uptake by normal hepatocytes in vitro and in vivo. Therefore, this study not only developed a simple yet efficient strategy toward a facile fabrication of NPs with dual-targeting ligands but also presented a precise therapeutic platform for HCC with great potential for clinical translation.
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