title: Role of scavenger receptors in peptide-based delivery of plasmid DNA across a blood-brain barrier model.
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.
authors.affiliation: 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.
authors.forename: Artita
authors.initials: A
authors.lastname: Srimanee
authors.affiliation: Department of Neurochemistry, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Regberg
authors.affiliation: Department of Neurochemistry, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Hällbrink
authors.affiliation: Excellent Center for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Rd., 10400 Bangkok, Thailand.
authors.forename: Opa
authors.initials: O
authors.lastname: Vajragupta
authors.affiliation: 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.
authors.forename: Ülo
authors.initials: Ü
authors.lastname: Langel
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D010957:Plasmids; D051116:Receptors, Scavenger / Q000378:metabolism*
chemical_list: D010455:Peptides; D051116:Receptors, Scavenger; D004247:DNA
keywords: Blood–brain barrier; LRP-1 receptor; Plasmid transfection; Receptor-mediated endocytosis; Scavenger receptors; angiopep-2; bEnd.3