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مقالات فارسیISIکنفرانسهاژورنالها

Nanolipoparticles-mediated MDR۱ siRNA delivery reduces doxorubicin resistance in breast cancer cells and silences MDR۱ expression in xenograft model of human breast cancer

محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 18، شماره: 4
سال انتشار: 1394
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 199

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لینک ثابت به این مقاله:
https://civilica.com/doc/1297152

شناسه ملی سند علمی:

JR_IJBMS-18-4_011

تاریخ نمایه سازی: 3 آبان 1400

چکیده 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 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 targeting

نویسندگان

Mahnaz Nourbakhsh

Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Mahmoud Reza Jaafari

Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Hermann Lage

Charite´ Campus Mitte, Institute of Pathology, Charite´platz ۱, D-۱۰۱۱۷ Berlin, Germany

Khalil Abnous

Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Fatemeh mosaffa

Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Ali Badiee

Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Javad Behravan

Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

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