It has been reported that in Alzheimer's disease, the amyloid Ab peptide tends to reach a concentration equilibrium between brain tissue and blood. For this reason, Ab sequestration in blood was proposed as a mean to maintain its tissue-blood concentration gradient thus favoring its removal from the brain ("sink" effect). We investigated the effects of NPs functionalized with cardiolipin (CL) or phosphatidic acid (PA) in order to target the sequence Ab1–42 peptide on the barrier properties of HUVEC monolayer. HUVEC cells incubated with NPs were evaluated for their viability and for monolayer integrity.

After 24 hours of incubation, 1 mM CL- or PA-NPs formulation caused up to 30% of cellular distress (MTT test and LDH release assay), therefore we exposed HUVEC cells to 200mM. Cells increased nitric oxide (NO) production by 60%±8.1 for CL and 82%±7.6 for PA, relative to control; the transendothelial permeability moreover, decreased by 13.2%±0.03 for CL (p<0.05) and 22.6%± 0.07 for PA (p<0.05 relative to control and to CL). Immunocytochemistry showed a decreased expression of a marker of tight junctions (ZO-1) by 11%± 0.06 for CL (p<0.05) and 14%± 0.05 for PA (p<0.05 relative to control and to CL).

We conclude that the increase in NO production by PA-NPs is in line with a significant greater increase in barrier permeability and weakening of tight junctions. Therefore, the effect of PA-NPs on endothelial barrier properties favors the Ab withdrawal from the brain.