title: Investigation of the therapeutic efficacy of codelivery of psiRNA-vascular endothelial growth factor and pIL-4 into chitosan nanoparticles in the breast tumor model.
abstract: Angiogenesis has been known to increase tumor growth and for its metastatic potential in human tumors. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is a promising therapeutic target for breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits tumor growth and migration in rats. The purpose of the present study was to improve therapeutic efficacy in breast cancer with the codelivery of siRNA-expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene-silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study breast tumor model demonstrated that the administration of coencapsulation of psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone. These results indicate that chitosan NPs can be effectively used for the codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy against breast cancer.
authors.affiliation: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, İnönü University, Malatya, Turkey.
authors.forename: Emine
authors.initials: E
authors.lastname: Şalva
authors.forename: Suna O
authors.initials: SO
authors.lastname: Turan
authors.forename: Levent
authors.initials: L
authors.lastname: Kabasakal
authors.forename: Saadet
authors.initials: S
authors.lastname: Alan
authors.forename: Naziye
authors.initials: N
authors.lastname: Özkan
authors.forename: Fatih
authors.initials: F
authors.lastname: Eren
authors.forename: Jülide
authors.initials: J
authors.lastname: Akbuğa
mesh_terms: D000818:Animals; D001940:Breast / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006801:Humans; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014162:Transfection; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: C508598:IL4 protein, human; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D015847:Interleukin-4; D048271:Chitosan
keywords: IL-4; RNA interference; VEGF; breast cancer; chitosan nanoparticles