Anti-A尾-MAb and dually decorated nanoliposomes: Effect of A尾1-42 peptides on interaction with hCMEC/D3 cells

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• 作者：Eleni Markoutsa^a ; Konstantina Papadia^a ; Carla Clemente^b ; Orfeu Flores^b ; Sophia G. Antimisiaris^a ; ^c ; ^{santimis@upatras.gr}
• 关键词：Targeting ; Amyloid ; Abeta peptides ; RAGE ; Blood&ndash ; brain barrier ; Transcytosis
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2012
• 期刊代码：16_09396411
• 类别：pha
• 出版时间：May, 2012
• 卷：81
• 期：1
• 页码：49-56
• 文件大小：548 K

摘要

Anti-A尾-MAb (A尾-MAb)-decorated immunoliposomes (LIP) and dually decorated ones (dd-LIP) with OX-26 and A尾-MAb were constructed. In both cases, the biotin-streptavidin ligation method was applied. All LIP types were characterized for size distribution, zeta potential, and integrity during incubation with serum proteins. Uptake and transcytosis of both LIP types and control vesicles by human brain endothelial hCMEC/D3 cells were measured. All LIP types had mean diameters below 150-200 nm and low polydispersity. A尾-MAb-LIP uptake was higher than control PEGylated liposomes, while uptake of dd-LIP was similar to that of OX-26-LIP. A尾-MAb-LIP and dd-LIP uptake increased significantly when cells were pre-incubated with A尾1-42 peptides; OX-26-LIP uptake was not modulated. Transcytosis of A尾-MAb-LIP through monolayers was 2.5 times higher when monolayers were pre-incubated with A尾1-42. Transport of both probes, FITC-dextran and rhodamine-lipid, was equivalent, indicating that A尾-MAb-LIP are transferred intact through the BBB model. The A尾 peptide-induced increase in binding (and transport) is regulated by the membrane receptors for A尾1-42 peptides (RAGE), as proven after blocking RAGE by a specific MAb. A尾1-42 peptides did not modulate the barrier tightness and integrity, as determined by transendothelial resistance and Lucifer Yellow permeability. Additionally, hCMEC/D3 cell viability was not affected by A尾 peptides or by A尾-MAb-LIP.