1. Investigation of the therapeutic efficacy of codelivery of psiRNA-vascular endothelial growth factor and pIL-4 into chitosan nanoparticles in the breast tumor model.
- Author
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Şalva E, Turan SO, Kabasakal L, Alan S, Özkan N, Eren F, and Akbuğa J
- Subjects
- Animals, Breast blood supply, Breast metabolism, Breast pathology, Breast Neoplasms metabolism, Breast Neoplasms pathology, Chitosan administration & dosage, Chitosan chemistry, Female, Humans, Injections, Intraperitoneal, Interleukin-4 chemistry, Interleukin-4 genetics, Interleukin-4 metabolism, MCF-7 Cells, Nanoparticles chemistry, Neovascularization, Pathologic metabolism, Neovascularization, Pathologic pathology, Neovascularization, Pathologic prevention & control, Plasmids administration & dosage, Plasmids chemistry, Plasmids metabolism, RNA, Small Interfering chemistry, RNA, Small Interfering metabolism, Random Allocation, Rats, Rats, Sprague-Dawley, Solubility, Transfection, Tumor Burden, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Breast Neoplasms therapy, Gene Silencing, Gene Transfer Techniques, Interleukin-4 therapeutic use, Nanoparticles administration & dosage, RNA, Small Interfering therapeutic use, Vascular Endothelial Growth Factor A antagonists & inhibitors
- 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., (© 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.)
- Published
- 2014
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