title: Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy.
abstract: Therapeutic antiangiogenesis strategies have demonstrated significant antitumor efficacy in ovarian cancer. Recently, RNA interference (RNAi) has come to be regarded as a promising technology for treatment of disease, especially cancer. In this study, vascular endothelial growth factor (VEGF)-small interfering RNA (siRNA) was encapsulated into a magnetic mesoporous silica nanoparticle (M-MSN)-based, polyethylenimine (PEI)-capped, polyethylene glycol (PEG)-grafted, fusogenic peptide (KALA)-functionalized siRNA delivery system, termed M-MSN_VEGF siRNA@PEI-PEG-KALA, which showed significant effectiveness with regard to VEGF gene silencing in vitro and in vivo. The prepared siRNA delivery system readily exhibited cellular internalization and ease of endosomal escape, resulting in excellent RNAi efficacy without associated cytotoxicity in SKOV3 cells. In in vivo experiments, notable retardation of tumor growth was observed in orthotopic ovarian tumor-bearing mice, which was attributed to significant inhibition of angiogenesis by systemic administration of this nanocarrier. No obvious toxic drug responses were detected in major organs. Further, the magnetic core of M-MSN_VEGF siRNA@PEI-PEG-KALA proved capable of probing the site and size of the ovarian cancer in mice on magnetic resonance imaging. Collectively, the results demonstrate that an M-MSN-based delivery system has potential to serve as a carrier of siRNA therapeutics in ovarian cancer.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China ; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China ; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, People's Republic of China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China ; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China ; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Ding Sheng-Zi
authors.initials: DS
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China ; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, People's Republic of China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China ; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Hongchen
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China ; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Di
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D020533:Angiogenesis Inhibitors; D058185:Magnetite Nanoparticles; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A
keywords: antiangiogenesis; mesoporous silica nanoparticles; ovarian cancer; small interfering RNA; vascular endothelial growth factor
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