Polybutylcyanoacrylate nanoparticles as novel vectors in cancer gene therapy.
To make progress toward an efficient gene vector for cancer gene therapy, a novel nonviral vector of polybutylcyanoacrylate nanoparticles (PBCA NPs) was developed. Cetyltrimethyl ammonium bromide (CTAB) was used to modify the surface of PBCA NPs, and then the plasmid DNA (pDNA) of pAFP-TK was wrapped into PBCA-CTAB NPs. Atomic force microscopy and zeta potential demonstrated that PBCA-CTAB NPs were 80-200 nm in diameter and had +15.6 mV positive surface charges. Assay using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide showed that PBCA-CTAB NPs had less cytotoxicity to 3T3 cells than HepG2 cells. The analysis of PBCA-CTAB-DNA complexes could not only protect DNA from degradation by DNase I, it could also transfer pDNA into targeted cells with high transfection efficiency. Furthermore, when PBCA-CTAB NPs combined with suicide gene pAFP-TK, alpha-fetoprotein-positive cells transfected by it were highly sensitive to ganciclovir treatment, and cell survival declined precipitously. Therefore, this target strategy using a pAFP-TK/GCV suicide gene therapy system in which PBCA-CTAB NPs serve as gene delivery vectors explores a promising area for alpha-fetoprotein-positive hepatocellular carcinoma and associated carcinoma therapy.
Zhang
Yangde
Y
National Hepatobiliary and Enteric Surgery Research Center, Central South University, Changsha, Hunan, China.
Zhang
Yanqiong
Y
Chen
Jiji
J
Zhang
Binghua
B
Pan
Yifeng
Y
Ren
Lifeng
L
Zhao
Jinfen
J
Luo
Yulin
Y
Zhai
Denggao
D
Wang
Shunwei
S
Wang
Jiwei
J
D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics*; D004337:Drug Carriers / Q000737:chemistry*; D004659:Enbucrilate / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000628:therapy; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D014162:Transfection / Q000379:methods*
D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D004247:DNA; D004659:Enbucrilate