Authors
Wei Zhang, Nathan Smith, Eduardo A Veliz, Bowen Zhao, Nabin Kandel, Annu Joji, Jiuyan Chen, Braulio C L B Ferreira, Miranda Perez, Xiomara Claure, Yiqun Zhou, Keenan J Mintz, Fuwu Zhang, Chunyu Wang, Roger M Leblanc
Published in
Colloids and surfaces. B, Biointerfaces. Pages 116175. Sep 11, 2026. Epub Sep 11, 2026.
Abstract
Tau aggregation is a pathological hallmark of Alzheimer's disease, yet small-molecule inhibitors targeting this process often face limitations in solubility, selectivity, and bioavailability. In this study, we engineered a library of hybrid nanostructures by covalently conjugating eleven structurally diverse chalcone derivatives to carbon nitride dots (CNDs), aiming to enhance their physicochemical stability and therapeutic efficacy. The resulting CND-chalcone conjugates exhibited favorable aqueous dispersibility and minimal cytotoxicity in HEK293 and HeLa cells. In vitro aggregation assays revealed that the conjugates modulated tau fibrillization in a structure-dependent manner, with several hybrids, particularly those containing hydroxyl or selectively positioned methoxy groups, showing strong inhibitory effects. Thioflavin-T fluorescence assays confirmed that the most active conjugates disrupted both nucleation and elongation phases of fibril formation. Notably, one hybrid (CNDs-S6) outperformed its free chalcone counterpart, suggesting synergistic interactions between the nanoparticle platform and ligand. These findings highlight the potential of CND-chalcone architectures as multifunctional nanoinhibitors and offer a rational approach to designing aggregation-targeting nanotherapeutics for neurodegenerative disease intervention.
PMID:
42767917
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.
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