Intracerebral Nanoparticle Transport Facilitated by Alzheimer Pathology and Age
Open accessAbstract
Nanoparticles have emerged as potential transporters of drugs targeting Alzheimer's disease (AD), but their design should consider the blood-brain barrier (BBB) integrity and neuroinflammation of the AD brain. This study presents that aging is a significant factor for the brain localization and retention of nanoparticles, which we engineered to bind with reactive astrocytes and activated microglia. We assembled 200 nm-diameter particles using a block copolymer of poly(lactic-co-glycolic acid) (PLGA) and CD44-binding hyaluronic acid (HA). The resulting PLGA-b-HA nanoparticles displayed increased binding to CD44-expressing reactive astrocytes and activated microglia. Upon intravascular injection, nanoparticles were localized to the hippocampi of both APP/PS1 AD model mice and their control littermates at 13-16 months of age due to enhanced transvascular transport through the leaky BBB. No particles were found in the hippocampi of young adult mice. These findings demonstrate the brain localization of nanoparticles due to aging-induced BBB breakdown regardless of AD pathology.
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Nanoparticles designed to target Aβ plaques and anti-inflammatory pathways have shown higher bioavailability and effectiveness in early-stage Alzheimer's disease.
“During this phase, NPs designed to target Aβ plaques—a key feature of AD—as well as anti-inflammatory pathways, have shown higher bioavailability and effectiveness [80, 144].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [144]
The paper’s Abstract (page unavailable) reports increased brain localization of nanoparticles designed to bind inflammation-associated astrocytes and microglia in aged mice, which supports a limited transport-related part of the claim. It does not show targeting of Aβ plaques or anti-inflammatory pathways, improved therapeutic effectiveness, or higher bioavailability in early-stage Alzheimer’s disease; localization was minimal in young adult mice. (LLM, conf=0.88)
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Targeted HA@Que-Mn nanozymes alleviate postherpetic neuralgia by modulating neuroinflammation
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Developing precision nanoparticle-based drug delivery systems for Alzheimer's disease therapy
Shan, Q., Zheng, W., Yao, W., Bai, Y., Ding, W., Wang, J., & Bai, F. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.103789
- Authors
- Tracy, G. C., Huang, K.-Y., Hong, Y.-T., Ding, S., Noblet, H. A., Lim, K. H., Kim, E. C., Chung, H. J., & Kong, H.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Chung, Hee Jung
- Kong, Hyunjoon
- Venue
- Nano Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-11-22
- Volume
- 23
- Issue
- 23
- Pages
- 10971-10982
- ISSN
- 1530-6984 (ISSN-L)
- 1530-6992
- PMC
- PMC11404402
- OpenAlex
- W4388906784
- Cited by
- 24
- References
- 73
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 7
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nano Letters (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01 NS083402, R01 NS097610, R01 NS100019)
- National Heart, Lung, and Blood Institute (NIH R61HL159948)
- Alzheimer's Association (2019-AARG-NTF-644507)
- Campus Research Board (RB 19060)
- Chan Zuckerberg Biohub Chicago Acceleration Research Award
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, aging, blood-brain barrier disruption, CD44, hyaluronic acid, PLGA nanoparticles, reactive astrocytes, activated microglia, hippocampus, APP/PS1 mice, neuroinflammation
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Alzheimer Disease, Animals, Blood-Brain Barrier, Brain, Mice, Transgenic, Mice, Nanoparticles
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