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Gal-CMCS-Fe3O4-NPs are galactose-conjugated carboxymethyl chitosan-coated magnetic iron oxide nanoparticles designed as a dual-targeting gene delivery system for hepatocellular carcinoma (HCC). The nanoparticles utilize **galactose ligands** for specific targeting to asialoglycoprotein receptors (ASGPR) overexpressed on liver cells and HCC cells, combined with **magnetic targeting** capability provided by Fe3O4 cores that allow external magnetic field-guided accumulation at tumor sites. The system is based on **carboxymethyl chitosan (CMCS)**, which offers superior biocompatibility and biodegradability compared to regular chitosan. The nanoparticles have a mean hydrodynamic size of approximately 40 nm with a positive zeta potential of +6.5 mV, enabling efficient DNA condensation and cellular uptake. In preclinical studies, Gal-CMCS-Fe3O4-NPs demonstrated high selectivity for HCC cells and liver cells in vitro, specific accumulation in HCC tissue in vivo (especially with external magnetic field assistance), and successful delivery of therapeutic genes such as RASSF1A for cancer treatment. The system showed minimal hemolysis (below 2%), low cytotoxicity with cell viability above 95% at 200 μg/ml concentration, and no acute toxic reactions in animal models. This nanomedicine platform was developed for targeted gene therapy applications in hepatocellular carcinoma.
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