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

作者：Markoutsa Eleni; Papadia Konstantina; Clemente Carla; Flores Orfeu; Antimisiaris Sophia G^*

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2012, 81(1): 49-56.

DOI：10.1016/j.ejpb.2012.02.006

• Targeting
• Amyloid
• Abeta peptides
• RAGE
• Blood-brain barrier
• Transcytosis

Anti-A beta-MAb (A beta-MAb)-decorated immunoliposomes (LIP) and dually decorated ones (dd-LIP) with OX-26 and A beta-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 beta-MAb-LIP uptake was higher than control PEGylated liposomes, while uptake of dd-LIP was similar to that of OX-26-LIP. A beta-MAb-LIP and dd-LIP uptake increased significantly when cells were pre-incubated with A beta 1-42 peptides; OX-26-LIP uptake was not modulated. Transcytosis of A beta-MAb-LIP through monolayers was 2.5 times higher when monolayers were pre-incubated with A beta 1-42. Transport of both probes, FITC-dextran and rhodamine-lipid, was equivalent, indicating that A beta-MAb-LIP are transferred intact through the BBB model. The A beta peptide-induced increase in binding (and transport) is regulated by the membrane receptors for A beta 1-42 peptides (RAGE), as proven after blocking RAGE by a specific MAb. A beta 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 beta peptides or by A beta-MAb-LIP.

• 出版日期2012-5