Role of scavenger receptors in peptide-based delivery of plasmid DNA across a blood-brain barrier model
Number of Authors: 5
2016 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 500, no 1-2, 128-135 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2016. Vol. 500, no 1-2, 128-135 p.
Blood-brain barrier, bEnd.3, Plasmid transfection, Scavenger receptors, angiopep-2, LRP-1 receptor, Receptor-mediated endocytosis
Physical Chemistry Biochemistry and Molecular Biology Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:su:diva-128163DOI: 10.1016/j.ijpharm.2016.01.014ISI: 000370049900013PubMedID: 26773601OAI: oai:DiVA.org:su-128163DiVA: diva2:915151