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

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• 作者：Artita Srimanee^a ; ^b ; ^{artita.srimanee@neurochem.su.se" class="auth_mail" title="E-mail the corresponding author} ; Jakob Regberg^b ; Mattias Hä ; llbrink^b ; Opa Vajragupta^d ; Ü ; lo Langel^b ; ^c
• 关键词：PF ; PepFect ; BBB ; blood&ndash ; brain barrier ; ANG ; angiopep-2 ; CR ; charge ratio ; pGL3 ; luciferase-encoding plasmid ; SRs ; scavenger receptors ; TAE ; Tris&ndash ; acetate-EDTA ; TBE ; Tris&ndash ; borate-EDTA ; EtBr ; ethidium bromide
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：16 March 2016
• 年：2016
• 卷：500
• 期：1-2
• 页码：128-135
• 全文大小：906 K

文摘

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.