Asialoglycoprotein receptormagnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma

作者：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^*

来源：Scientific Reports, 2016, 6(1): 22149.

DOI：10.1038/srep22149

• IRON-OXIDE NANOPARTICLES
• TUMOR-SUPPRESSOR GENE
• BIOMEDICAL APPLICATIONS
• IN-VITRO
• PROMOTER HYPERMETHYLATION
• CHITOSAN
• THERAPY
• LIVER
• DNA
• CHEMOTHERAPY

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-Fe(3)O(4-)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.

• 出版日期2016-2-26
• 单位南通大学