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Peptide functionalization of a brain-targeting hybrid nanocarrier for enhanced drug transport in Alzheimer's disease
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DOI：10.1039/D6NJ01716A.png)
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Abstract
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To address the limited transport of therapeutics across the blood–brain barrier (BBB) in Alzheimer's disease (AD); we engineered brain targeting inorganic hybrid nanoparticles (TNP) capable of co-delivering curcumin (CUR) and quercetin (QUER) for AD treatment. TNP were surface functionalized with angiopep-2 via biotin–streptavidin interaction. The angiopep-2 peptide facilitates selective interaction with low-density lipoprotein receptor-related protein 1 (LRP1) expressed on endothelial cells; promoting receptor-mediated transport across the BBB. Additionally; angiopep-2 can promote the transport of drug loaded nanoparticles to affected neural cells by binding to LRP1; thereby enhancing drug accumulation in pathological regions of Alzheimer's disease. Compared with the free drugs; the co-delivery system CUR/QUER@TNP exerts neuroprotective effects; including antioxidant activity; inhibition of apoptosis; suppression of amyloid-β aggregation and modulation of tau protein phosphorylation; more effectively in SH-SY5Y cells. These results indicate that the brain targeting delivery system improves neuroprotective efficacy and leads to a more pronounced reduction in tau-associated pathology. Our study demonstrates that the inorganic hybrid nanocarrier can serve as an effective platform for enhancing brain drug delivery; thereby offering a promising avenue for AD therapy. This functionalization strategy; based on the biotin–streptavidin interaction; offers a facile and universal approach for the convenient incorporation of other targeting ligands.
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