Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma

• Published in: Scientific reports Vol. 6; no. 1; p. 22149
• Main Authors: Xue, Wan-Jiang, Feng, Ying, Wang, Fei, Guo, Yi-Bing, Li, Peng, Wang, Lei, Liu, Yi-Fei, Wang, Zhi-Wei, Yang, Yu-Min, Mao, Qin-Sheng
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 26.02.2016
• Subjects: Animals; Asialoglycoprotein Receptor - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - therapy; Caspase; Caspase-3; Cell Line, Tumor; Chitosan; Chitosan - analogs & derivatives; Chitosan - pharmacology; Deoxyribonucleic acid; DNA; Galactose; Gene transfer; Gene Transfer Techniques; Genetic Therapy - methods; Hep G2 Cells; Hepatocellular carcinoma; Hepatocytes; Hepatocytes - metabolism; Humans; Injection; Intravenous administration; Iron; Liver cancer; Liver Neoplasms - pathology; Liver Neoplasms - therapy; Magnetic fields; Magnetite Nanoparticles - chemistry; Magnetite Nanoparticles - therapeutic use; Mice; Mice, Inbred BALB C; Mice, Nude; Mitomycin; Nanoparticles; Neoplasm Transplantation; pH effects; Rodents; Transplantation, Heterologous; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumor Suppressor Proteins - therapeutic use; Tumors; Zeta potential
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep22149

We developed a nanovector with double targeting properties for efficiently delivering the tumor suppressor gene RASSF1A specifically into hepatocellular carcinoma (HCC) cells by preparing galactosylated-carboxymethyl chitosan-magnetic iron oxide nanoparticles (Gal-CMCS-Fe3O4-NPs). After conjugating galactose and CMCS to the surface of Fe3O4-NPs, we observed that Gal-CMCS-Fe3O4-NPs were round with a relatively stable zeta potential of +6.5 mV and an mean hydrodynamic size of 40.1 ± 5.3 nm. Gal-CMCS-Fe3O4-NPs had strong DNA condensing power in pH 7 solution and were largely nontoxic. In vitro experiments demonstrated that Gal-CMCS-Fe3O4-NPs were highly selective for HCC cells and liver cells. In vivo experiments showed the specific accumulation of Gal-CMCS-Fe3O4-NPs in HCC tissue, especially with the aid of an external magnetic field. Nude mice with orthotopically transplanted HCC received an intravenous injection of the Gal-CMCS-Fe3O4-NPs/pcDNA3.1(+)RASSF1A compound and intraperitoneal injection of mitomycin and had an external magnetic field applied to the tumor area. These mice had the smallest tumors, largest percentage of TUNEL-positive cells, and highest caspase-3 expression levels in tumor tissue compared to other groups of treated mice. These results suggest the potential application of Gal-CMCS-Fe3O4-NPs for RASSF1A gene delivery for the treatment of HCC.