Coassembled Chitosan-Hyaluronic Acid Nanoparticles as a Theranostic Agent Targeting Alzheimer's β-Amyloid

beta-Amyloid (A beta) fibrillogenesis is closely associated with the pathogenesis of Alzheimer's disease (AD), so detection and inhibition of A beta aggregation are of significance for the theranostics of AD. In this work, the coassembled nanoparticles of chitosan and hyaluronic acid cross-linked with glutaraldehyde (CHG NPs) were found to work as a theranostic agent for imaging/probing and inhibition of A beta fibrillization both in vitro and in vivo. The biomass-based CHG NPs of high stability exhibited a wide range of excitation/emission wavelengths and showed binding affinity toward A beta aggregates, especially for soluble A beta oligomers. CHG NPs displayed weak emission in the monodispersed state, while they remarkably emitted increased red fluorescence upon interacting with A beta oligomers and fibrils, showing high sensitivity with a detection limit of 0.1 nM. By comparing the different fluorescence responses of CHG NPs and Thioflavin T to A beta aggregation, the A beta oligomerization rate during nucleation can be determined. Moreover, the fluorescence recognition behavior of CHG NPs was selective. CHG NPs specifically bind to negatively charged amyloid aggregates but not to positively charged amyloids and negatively charged soluble proteins. Such enhancement in fluorescence emission is attributed to the clustering-triggered emission effect of CHG NPs after interaction with A beta aggregates via various electronic conjugations and hydrogen bonding, electrostatic, and hydrophobic interactions. Besides fluorescent imaging/ probing, CHG NPs over 360 mu g/mL could almost completely inhibit the formation of A beta fibrils, exhibiting the capability of regulating A beta aggregation. In-vivo assays with Caenorhabditis elegans CL2006 demonstrated the potency of CHG NPs as an effective theranostic nanoagent for imaging A beta plaques and inhibiting A beta deposition. The findings proved the potential of CHG NPs for development as a potent agent for the diagnosis and treatment of AD.

Automated summary

The coassembled nanoparticles of chitosan and hyaluronic acid cross-linked with glutaraldehyde (CHG NPs) were found to be an effective theranostic agent for imaging and inhibiting A beta fibrillization in Alzheimer's disease. The CHG NPs exhibited high sensitivity and selectivity in detecting A beta oligomers, showing potential for diagnosis and treatment of AD. In addition to fluorescence imaging, CHG NPs also demonstrated the capability to regulate A beta aggregation, making them a promising tool for theranostics in AD.