Protection against Neurodegeneration in the Hippocampus Using Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles

Jen Tsung Yang, Yung Chih Kuo*, I. Yin Chen, Rajendiran Rajesh, Yung I. Lou, Jyh Ping Hsu

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations


Significant 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-β (Aβ) 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 Aβ 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 Aβ accumulation, lipid peroxidation, and neuronal apoptosis for the AD management.

Original languageEnglish
Pages (from-to)1311-1320
Number of pages10
JournalACS Biomaterials Science and Engineering
Issue number3
StatePublished - 11 03 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.


  • 5-HT-moduline
  • lipopolymer
  • phosphatidic acid
  • poly(lactide- co-glycolide)
  • sialic acid


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