title: Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
authors.forename: Wan-Jiang
authors.initials: WJ
authors.lastname: Xue
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Surgical Comprehensive Laboratory, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226007, Jiangsu, China.|The Neural Regeneration Co-innovation Center of Jiangsu Province, Nantong University, Nantong 226007, Jiangsu, China.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong 226001, Jiangsu, China.
authors.forename: Qin-Sheng
authors.initials: QS
authors.lastname: Mao
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives* / Q000494:pharmacology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D037263:Asialoglycoprotein Receptor; D058185:Magnetite Nanoparticles; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C514968:carboxymethyl-chitosan; D048271:Chitosan