title: Tumor-targeting magnetic lipoplex delivery of short hairpin RNA suppresses IGF-1R overexpression of lung adenocarcinoma A549 cells in vitro and in vivo.
abstract: Liposomal magnetofection potentiates gene transfection by applying a magnetic field to concentrate magnetic lipoplexes onto target cells. Magnetic lipoplexes are self-assembling ternary complexes of cationic lipids with plasmid DNA associated with superparamagnetic iron oxide nanoparticles (SPIONs). Type1 insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently overexpressed in lung cancer and mediates cancer cell proliferation and tumor growth. In this study, we evaluated the transfection efficiency (percentage of transfected cells) and therapeutic potential (potency of IGF-1R knockdown) of liposomal magnetofection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) in A549 cells and in tumor-bearing mice as compared to lipofection using Lipofectamine 2000. Liposomal magnetofection provided a threefold improvement in transgene expression over lipofection and transfected up to 64.1% of A549 cells in vitro. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1±6% and by liposomal magnetofection by 85.1±3%. In vivo delivery efficiency of the pGFPshIGF-1R plasmid into the tumor was significantly higher in the liposomal magnetofection group than in the lipofection group. In vivo IGF-1R specific-shRNA by lipofection inhibited IGF-1R protein by an average of 43.8±5.3%; that by liposomal magnetofection inhibited IGF-1R protein by 43.4±5.7%, 56.3±9.6%, and 72.2±6.8%, at 24, 48, and 72 h, respectively, after pGFPshIGF-1R injection. Our findings indicate that liposomal magnetofection may be a promising method that allows the targeting of gene therapy to lung cancer.
authors.affiliation: Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, PR China.
authors.forename: Chunmao
authors.initials: C
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Ding
authors.forename: Minjian
authors.initials: M
authors.lastname: Kong
authors.forename: Aiqiang
authors.initials: A
authors.lastname: Dong
authors.forename: Jianfang
authors.initials: J
authors.lastname: Qian
authors.forename: Daming
authors.initials: D
authors.lastname: Jiang
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000628:therapy*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D055785:Gene Knockdown Techniques / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D034741:RNA, Small Interfering / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D014162:Transfection / Q000379:methods*
chemical_list: D058185:Magnetite Nanoparticles; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1