Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 19, Pages 21822-21835Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c00007
Keywords
oxytocin; Alzheimer ? s disease; microglial activation; neuroin fl ammation; chitosan nanogels
Funding
- National Natural Science Foundation of China [81871431, 82171905, 81801828]
- Tianjin Key Medical Discipline (Specialty) Construction Project
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Researchers developed oxytocin-loaded angiopep-2-modified chitosan nanogels (AOC NGs) to inhibit microglial activation and reduce neuroinflammation in the early stage of Alzheimer's disease. The nanogels successfully crossed the blood-brain barrier and effectively slowed disease progression, prevented cognitive impairment, and delayed hippocampal atrophy in mice.
Prevention of Alzheimer's disease (AD) is a global imperative, but reliable early interventions are currently lacking. Microglia-mediated chronic neuroinflammation is thought to occur in the early stage of AD and plays a critical role in AD pathogenesis. Here, oxytocin (OT)-loaded angiopep-2-modified chitosan nanogels (AOC NGs) were designed for early treatment of AD via inhibiting innate inflammatory response. Through the effective transcytosis of angiopep-2, AOC NGs were driven intravenously to cross the blood-brain barrier, enter the brain, and enrich in brain areas affected by AD. A large amount of OT was then released and specifically bound to the pathological upregulated OT receptor, thus effectively inhibiting microglial activation and reducing inflammatory cytokine levels through blocking the ERK/p38 MAPK and COX-2/iNOS NF-Kappa B signaling pathways. Consecutive weekly intravenous administration of AOC NGs into 12-week-old young APP/PS1 mice, representing the early stage of AD, remarkably slowed the progression of A beta deposition and neuronal apoptosis in the APP/PS1 mice as they aged and ultimately prevented cognitive impairment and delayed hippocampal atrophy. Together, the findings suggest that AOC NGs, which show good biosafety, can serve as a promising therapeutic candidate to combat neuroinflammation for early prevention of AD.
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