“Drug‐Carrier” Synergy Therapy for Amyloid‐β Clearance and Inhibition of Tau Phosphorylation via Biomimetic Lipid Nanocomposite Assembly
Open accessAbstract
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.
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APLN/MB "drug carrier" synergistic therapy is a promising approach for the development of Alzheimer's disease treatment.
“APLN/MB “drug carrier” synergistic therapy is a promising approach for the development of Alzheimer’s disease treatment [197].”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [197]
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Cited by
Sorted by citations
Yang, J., Zhi, W., & Wang, L. (2024) · Molecules · doi:10.3390/molecules29122812 · Cited by 63 · see citing works
“APLN/MB “drug carrier” synergistic therapy is a promising approach for the development of Alzheimer’s disease treatment [197].”
Background
- Authors
- Han, G., Bai, K., Yang, X., Sun, C., Ji, Y., Zhou, J., Zhang, H., & Ding, Y.
- Affiliations
- China Pharmaceutical University (CN)
- Corresponding author
- Zhou, Jianping
- Zhang, Huaqing
- Ding, Yang
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2022-03-20
- Volume
- 9
- Issue
- 14
- Pages
- e2106072-e2106072
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC9108666
- OpenAlex
- W4220986443
- Cited by
- 46
- References
- 57
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 16 · 2023: 9 · 2022: 5
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (82073401, 82104097, 81872819, 82073795)
- Natural Science Foundation of Jiangsu Province (BK20210426)
- China Postdoctoral Science Foundation (2020TQ0359, 2020M681790)
- Guizhou Medical University ([2022] 387)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- Alzheimer's disease, amyloid-beta clearance, tau phosphorylation, apolipoprotein A-I, Angiopep-2, methylene blue, blood-brain barrier penetration, drug delivery, cognitive function
- MeSH terms
- Alzheimer Disease, Animals, Drug Carriers, Lipids, Methylene Blue, Phosphorylation, Amyloid beta-Peptides, tau Proteins, Biomimetics, Mice, Nanocomposites
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