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Iranian Journal of Basic Medical Sciences، جلد ۱۸، شماره ۴، صفحات ۳۸۵-۳۹۲
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عنوان انگلیسی Nanolipoparticles-mediated MDR1 siRNA delivery reduces doxorubicin resistance in breast cancer cells and silences MDR1 expression in xenograft model of human breast cancer
چکیده انگلیسی مقاله 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 MDR1 in tumor cells more than 80%, while OFA had a reverse effect on MDR1 expression in vivo. Conclusion: The results indicated that the prepared NLPs could be suitable siRNA delivery systems for tumor therapy.
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نویسندگان مقاله مهناز نوربخش | mahnaz nourbakhsh
biotechnology research center, mashhad university of medical sciences, mashhad, iran|nanotechnology 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

سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)

محمودرضا جعفری | mahmoud reza jaafari
nanotechnology 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

سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)

hermann lage | hermann lage
charite campus mitte, institute of pathology, charite platz 1, d-10117 berlin, germany


خلیل abnous | khalil abnous
pharmaceutical research center, school of pharmacy, mashhad university of medical sciences, mashhad, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)

فاطمه مصفا | fatemeh mosaffa
department of pharmaceutical biotechnology, school of pharmacy, mashhad university of medical sciences, mashhad, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)

علی بدیعی | ali badiee
nanotechnology research center, school of pharmacy, mashhad university of medical sciences, mashhad, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)

جواد بهروان | javad behravan
biotechnology research center, mashhad university of medical sciences, mashhad, iran|department of pharmaceutical biotechnology, school of pharmacy, mashhad university of medical sciences, mashhad, iran.

سازمان اصلی تایید شده: دانشگاه علوم پزشکی مشهد (Mashhad university of medical sciences)

نشانی اینترنتی http://ijbms.mums.ac.ir/article_4288.html
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