title: Treating colon cancer with a suicide gene delivered by self-assembled cationic MPEG-PCL micelles.
abstract: Biodegradable cationic micelles show promise for applications in gene delivery. In this article, we used DOTAP to modify monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL, MP) micelles in one step, creating novel cationic self-assembled DOTAP and MPEG-PCL hybrid micelles (DMP). These micelles had a mean particle size of 46 ± 5.6 nm and a zeta potential of 41.8 ± 0.5 mV, and had the capacity to bind DNA. Compared with PEI25K (the gold standard), DMP micelles had higher transfection efficiency and lower cytotoxicity. Moreover, we used DMP to deliver the Survivin-T34A gene (S-T34A, a suicide gene) to treat colon cancer. DMP delivered the Survivin-T34A gene (DMP/S-T34A) and could induce apoptosis in cancer cells, resulting in inhibition of the growth of C-26 colon cancer cells in vitro. An in vivo study indicated that intraperitoneal administration of DMP micelles delivered the Survivin-T34A gene and efficiently inhibited the growth of abdominal metastatic C-26 colon cancer and the malignant ascites. These data suggest that DMP may be a novel gene carrier, and its delivery of the S-T34A gene may have promising applications in the treatment of colon cancer.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
authors.forename: XingMei
authors.initials: X
authors.lastname: Duan
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Men
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: MeiJuan
authors.initials: M
authors.lastname: Huang
authors.forename: MaLing
authors.initials: M
authors.lastname: Gou
authors.forename: LiJuan
authors.initials: L
authors.lastname: Chen
authors.forename: ZhiYong
authors.initials: Z
authors.lastname: Qian
authors.forename: YuQuan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000628:therapy*; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000628:therapy*; D016503:Drug Delivery Systems; D005260:Female; D018014:Gene Transfer Techniques / Q000295:instrumentation; D041722:Genes, Transgenic, Suicide / Q000235:genetics; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods*; D005822:Genetic Vectors / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D008954:Models, Biological; D011091:Polyesters / Q000008:administration & dosage / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D014162:Transfection / Q000295:instrumentation / Q000379:methods
chemical_list: D008823:Micelles; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols