Nanolipoparticles-mediated MDR۱ siRNA delivery reduces doxorubicin resistance in breast cancer cells and silences MDR۱ expression in xenograft model of human breast cancer
- سال انتشار: 1394
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 18، شماره: 4
- کد COI اختصاصی: JR_IJBMS-18-4_011
- زبان مقاله: انگلیسی
- تعداد مشاهده: 215
نویسندگان
Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Charite´ Campus Mitte, Institute of Pathology, Charite´platz ۱, D-۱۰۱۱۷ Berlin, Germany
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
چکیده
Objective(s): P-glycoprotein (P-gp) is an efflux protein, the overexpression of which has been associated with multidrug resistance in various cancers. Although siRNA delivery to reverse P-gp expression may be promising for sensitizing of tumor cells to cytotoxic drugs, the therapeutic use of siRNA requires effective carriers that can deliver siRNA intracellularly with minimal toxicity on target cells. We investigated a special class of PEGylated lipid-based nanoparticles (NP), named nanolipoparticles (NLPs), for siRNA-mediated P-gp downregulation. Materials and Methods: NLPs were prepared based on low detergent dialysis method. After characterization, we evaluated the effect of NLPs on siRNA delivery, and P-gp downregulation compared to oligofectamineTM (OFA) in vitro and in vivo. Results: Our results showed a significant decrease in P-gp expression and subsequent enhancement of chemosensitivity to doxorubicin in vitro. Although the effectiveness of NLPs for in vitro siRNA delivery compared to OFA was limited, the results of in vivo studies showed noticeable effectiveness of NLPs for systemic siRNA delivery. siRNA delivery using NLPs could downregulate MDR۱ in tumor cells more than ۸۰%, while OFA had a reverse effect on MDR۱ expression in vivo. Conclusion: The results indicated that the prepared NLPs could be suitable siRNA delivery systems for tumor therapy.کلیدواژه ها
Breast Cancer, Gene Therapy, Liposome, Multidrug resistance, siRNA delivery, Tumor targetingاطلاعات بیشتر در مورد COI
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