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"Drug-Carrier" Synergy Therapy for Amyloid-β Clearance and Inhibition of Tau Phosphorylation via Biomimetic Lipid Nanocomposite Assembly.
- Source :
-
Advanced Science . 5/16/2022, Vol. 9 Issue 14, p1-14. 14p. - Publication Year :
- 2022
-
Abstract
- Amyloid-𝜷 (A𝜷) toxicity is considered to be companioned by Tau phosphorylation in Alzheimer's disease (AD). The clinical AD therapy is usually subjected to low blood-brain barrier (BBB) penetration and complex interaction mechanisms between A𝜷 and phosphorylated Tau. A "Drug-Carrier" synergy therapy is herein designed to simultaneously target A𝜷 and Tau-associated pathways for AD treatment. To imitate natural nanoparticle configuration, the endogenous apolipoprotein A-I and its mimicking peptide 4F fused angiopep-2 (Ang) are sequentially grafted onto lipid nanocomposite (APLN), providing liberty of BBB crossing and microglia targeted A𝜷 clearance. For synergy treatment, methylene blue (MB) is further assembled into APLN (APLN/MB) for Tau aggregation inhibition. After intravenous administration, the optimized density (5 wt%) of Ang ligands dramatically enhances APLN/MB intracerebral shuttling and accumulation, which is 2.15-fold higher than that Ang absent-modification. The site-specific release of MB collaborates APLN to promote A𝜷 capture for microglia endocytosis clearance and reduce p-Tau level by 25.31% in AD pathogenesis. In AD-A𝜷-Tau bearing mouse models, APLN/MB can relieve AD symptoms, rescue neuron viability and cognitive functions. Collectively, it is confirmed that "Drug-Carrier" synergy therapy of APLN/MB is a promising approach in the development of AD treatments. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 21983844
- Volume :
- 9
- Issue :
- 14
- Database :
- Academic Search Index
- Journal :
- Advanced Science
- Publication Type :
- Academic Journal
- Accession number :
- 157511963
- Full Text :
- https://doi.org/10.1002/advs.202106072