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Int J Pharm. 2016 Mar 16;500(1-2):128-35. doi: 10.1016/j.ijpharm.2016.01.014. Epub 2016 Jan 7.

Role of scavenger receptors in peptide-based delivery of plasmid DNA across a blood-brain barrier model.

Author information

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Rd., 10400 Bangkok, Thailand; Department of Neurochemistry, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden. Electronic address: artita.srimanee@neurochem.su.se.
2
Department of Neurochemistry, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden.
3
Excellent Center for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Rd., 10400 Bangkok, Thailand.
4
Department of Neurochemistry, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden; Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.

Abstract

Receptor-mediated transcytosis remains a major route for drug delivery across the blood-brain barrier (BBB). PepFect 32 (PF32), a peptide-based vector modified with targeting ligand (Angiopep-2) binding to low-density lipoprotein receptor-related protein-1 (LRP-1), was previously found to be a promising vector for plasmid delivery across an in vitro model of the BBB. Cellular uptake of PF32/plasmid DNA (pDNA) complexes was speculated the internalization via LRP-1 receptor. In this study, we prove that PF32/pDNA nanocomplexes are not only transported into brain endothelial cells via LRP-1 receptor-mediated endocytosis, but also via scavenger receptor class A and B (SCARA3, SCARA5, and SR-BI)-mediated endocytosis. SCARA3, SCARA5, and SR-BI are found to be expressed in the brain endothelial cells. Inhibition of these receptors leads to a reduction of the transfection. In conclusion, this study shows that scavenger receptors also play an essential role in the cellular uptake of the PF32/pDNA nanocomplexes.

KEYWORDS:

Blood–brain barrier; LRP-1 receptor; Plasmid transfection; Receptor-mediated endocytosis; Scavenger receptors; angiopep-2; bEnd.3

PMID:
26773601
DOI:
10.1016/j.ijpharm.2016.01.014
[Indexed for MEDLINE]

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