Materials today. BioSep 6, 2026

Nanoparticles carrying Panax notoginseng polysaccharides reduce Alzheimer's symptoms by changing immune cell metabolism through energy and oxygen sensing pathways

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 7, 2026

Abstract

KPBIT@NPs restore cerebral energy metabolism and significantly reduce amyloid-β deposition in Alzheimer's disease animal models.

KPBIT@NPs are designed as a dual-functional, responsive nanoparticle platform using a natural polysaccharide.
These nanoparticles enable the efficient co-loading of therapeutic agents and disassemble in response to pathological reactive oxygen species.
Surface modification with a specific peptide enhances transport across the blood-brain barrier and targeting of activated microglia.
The treatment activates a specific energy-sensing pathway and suppresses a signaling axis associated with inflammation and metabolism.
This coordinated response shifts microglia from a harmful, inflammatory state to a reparative phenotype.
In animal models of Alzheimer's disease, KPBIT@NPs alleviate neuroinflammation and improve cognitive function.

Simplified

Alzheimer's disease (AD) is increasingly recognized as an immunometabolic disorder characterized by a self-reinforcing cycle of neuroinflammation and glycolytic reprogramming in microglia. Herein, we developed KPBIT@NPs, a microglia-targeted polysaccharide-based nanomedicine. Unlike many conventional nanocarriers that mainly serve as passive delivery vehicles, KPBIT@NPs employ the natural macromolecule Panax notoginseng polysaccharide (PNP) to construct a dual-functional, responsive nanoparticle platform. Through rational engineering via phenylboronic ester grafting, the polysaccharide backbone enables amphiphilic self-assembly and efficient co-loading of icaritin and tanshinone IIA, while allowing pathological reactive oxygen species (ROS)-triggered disassembly. In addition, surface decoration with the KLVFFAED peptide facilitates blood-brain barrier transport and targeted accumulation in activated microglia. Mechanistically, KPBIT@NPs activate AMP-activated protein kinase and suppress the mechanistic target of rapamycin/hypoxia-inducible factor 1α signaling axis, thereby reversing pathological glycolytic skewing and restoring mitochondrial oxidative metabolism. This coordinated regulation disrupts the inflammation-metabolism feed-forward loop and successfully reprograms microglia from a pro-inflammatory, metabolically stressed state toward a reparative phenotype. In AD animal models, KPBIT@NPs effectively restore cerebral energy metabolism, markedly reduce amyloid-β deposition, alleviate neuroinflammation, preserve neuronal integrity, and ultimately rescue cognitive deficits. This study establishes an innovative nanotherapeutic paradigm based on bioactive polysaccharides and offers a promising materials strategy for neurodegenerative diseases driven by coupled metabolic and inflammatory dysregulation.

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Nanoparticles carrying Panax notoginseng polysaccharides reduce Alzheimer's symptoms by changing immune cell metabolism through energy and oxygen sensing pathways

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