Yang J.-T.Kuo Y.-C.Chen I.-Y.Rajesh R.Lou Y.-I.Hsu J.-P.2019-05-202019-05-20201923739878https://scholars.lib.ntu.edu.tw/handle/123456789/409216Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease. Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-£] (A£]) deposits. Morphological studies revealed a uniform exterior of QU-SA-5HTM-PA-PLGA NPs with a spherical structure and enhanced aggregation with inclusion of PA in the formulation. A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively. Immunofluorescence staining images also supported QU-SA-5HTM-PA-PLGA NPs to traverse the microvessels of AD rat brain. Western blot analysis showed that QU-loaded PA-PLGA NPs suppressed caspase-3 expression. The ability of the nanocarriers to recognize A£] fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus. Hence, the medication of QU-SA-5HTM-PA-PLGA NPs can facilitate the BBB penetration and prevent A£] accumulation, lipid peroxidation, and neuronal apoptosis for the AD management. ? 2019 American Chemical Society.5-HT-modulinelipopolymerphosphatidic acidpoly(lactide- co-glycolide)sialic acid[SDGs]SDG3Carboxylic acids; Cell death; Disease control; Electrophoresis; Nanoparticles; Oxidative stress; 5-HT-moduline; Lipo-polymer; Phosphatidic acids; Poly lactide-co-glycolide; Sialic acids; Neurodegenerative diseases; acetylcholinesterase; amyloid beta protein; caspase 3; leucylserylalanylleucine; malonaldehyde; n acetylglucosamine; phosphatidic acid; polyglactin; quercetin; serotonin; serotonin 1B receptor; sialic acid; Alzheimer disease; animal experiment; animal model; animal tissue; antioxidant activity; Article; blood brain barrier; controlled study; drug delivery system; drug formulation; drug penetration; electric resistance; hippocampus; human; human cell; immunofluorescence test; lipid peroxidation; male; membrane permeability; microvasculature; nerve degeneration; neuroapoptosis; neuroprotection; nonhuman; oxidative stress; particle size; priority journal; protein expression; rat; senile plaque; Western blotting; zeta potentialjournal article10.1021/acsbiomaterials.8b013342-s2.0-85062540336https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062540336&doi=10.1021%2facsbiomaterials.8b01334&partnerID=40&md5=b7b4568ac931ee2621907c12ea76ee16