title: Folate-Functionalized Magnetic-Mesoporous Silica Nanoparticles for Drug/Gene Codelivery To Potentiate the Antitumor Efficacy.
abstract: An appropriate codelivery system for chemotherapeutic agents and nucleic acid drugs will provide a more efficacious approach for the treatment of cancer. Combining gene therapy with chemotherapeutics in a single delivery system is more effective than individual delivery systems carrying either gene or drug. In this work, we developed folate (FA) receptor targeted magnetic-mesoporous silica nanoparticles for the codelivery of VEGF shRNA and doxorubicin (DOX) (denoted as M-MSN(DOX)/PEI-FA/VEGF shRNA). Our data showed that M-MSN(DOX)/PEI-FA could strongly condense VEGF shRNA at weight ratios of 30:1, and possesses higher stability against DNase I digestion and sodium heparin. In vitro antitumor activity assays revealed that HeLa cell growth was significantly inhibited. The intracellular accumulation of DOX by confocal microscopy and fluorescence spectrophotometry showed that M-MSN(DOX)/PEI-FA were more easily taken up than nontargeted M-MSN(DOX). Quantitative PCR and ELISA data revealed that M-MSN/PEI-FA/VEGF shRNA induced a significant decrease in VEGF expression as compared to cells treated with either the control or other complexes. The invasion and migration phenotypes of the HUVECs were significantly decrease after coculture with MSN/PEI-FA/VEGF shRNA nanocomplexes-treated HeLa cells. The approach provides a potential strategy to treat cancer by a singular nanoparticle delivery system.
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Shun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Biophysics, School of Life Science and Technology, ‡Center for Information in Medicine, University of Electronic Science and Technology of China , Chengdu 610054, Sichuan, People's Republic of China.
authors.forename: Yiyao
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D058972:Folic Acid Transporters / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D012822:Silicon Dioxide / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D058972:Folic Acid Transporters; D042461:Vascular Endothelial Growth Factor A; D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: DOX; M-MSN; VEGF shRNA; antiangiogenesis; codelivery