title: Nanolipoparticles-mediated MDR1 siRNA delivery reduces doxorubicin resistance in breast cancer cells and silences MDR1 expression in xenograft model of human breast cancer.
abstract: OBJECTIVE
  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.
  
  
  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 oligofectamine™ (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.
  
  
  CONCLUSIONS
  The results indicated that the prepared NLPs could be suitable siRNA delivery systems for tumor therapy.
authors.affiliation: 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.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Nourbakhsh
authors.affiliation: 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.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
authors.affiliation: Charite´ Campus Mitte, Institute of Pathology, Charite´platz 1, D-10117 Berlin, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Lage
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mosaffa
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran ; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Behravan
keywords: Breast cancer; Gene therapy; Liposome; Multidrug resistance; Tumor targeting; siRNA delivery