title: Tissue distribution and cancer growth inhibition of magnetic lipoplex-delivered type 1 insulin-like growth factor receptor shRNA in nude mice.
abstract: The targeted delivery of therapeutic genes into specific tissues, as well as the determination of the biological fate and potential toxicity of nanoparticles, remains a highly relevant challenge for gene-based therapies. Type 1 insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently over-expressed in lung cancer and mediates cancer cell proliferation as well as tumor growth. In our previous studies, we have successfully applied gene delivery mediated by commercially available nanoparticles (CombiMAG) under a magnetic field, which suppresses IGF-1R expression in a non-small cell lung cancer cell line (A549) in vitro. In the present study, we aimed to investigate the biological distribution and target tumor suppression of magnetofection, as well as its potential toxicity via CombiMAG-carrying plasmids expressing green fluorescent protein (GFP) and short hairpin RNAs (shRNAs) targeting IGF-1R (pGFPshIGF-1Rs) in tumor-bearing mice. The peak expression in various organs appeared 48 h after transfection. Transgene expression via magnetofection was 3-fold improvement than via lipofection. On the 30th day after injection, the tumor size and weight of the CombiMAG-treated group (789.32 ± 39.43 mm(3), 105.5 ± 6.1 mg) were significantly decreased compared with those of the lipofection group (893.83 ± 31.23 mm(3), 164.5 ± 9.1 mg; P< 0.05), and the suppression rate was ∼36%. After a 30-day observation, the injection of CombiMAG did not cause any apparent toxicity. Therefore, IGF-1R shRNA nanoparticles can be valuable and safe delivery agents for RNA interference therapy to tumors in vivo.
authors.affiliation: Department of Cardiovascular Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Minjian
authors.initials: M
authors.lastname: Kong
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Li
authors.forename: Chunmao
authors.initials: C
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Ding
authors.forename: Aiqiang
authors.initials: A
authors.lastname: Dong
authors.forename: Qunjun
authors.initials: Q
authors.lastname: Duan
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008055:Lipids / Q000737:chemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D060526:Magnetic Fields; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D008055:Lipids; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D017526:Receptor, IGF Type 1