The fibrillization and deposition of β‐amyloid protein (Aβ) are recognized to be the pathological hallmarks of Alzheimer's disease (AD), which signify the need for the effective detection and inhibition of Aβ accumulation. Development of multifunctional agents that can inhibit Aβ aggregation, rapidly disaggregate fibrils, and image aggregates is one of the effective strategies to treat and diagnose AD. Herein, the multifunctionality of nitrogen‐doped carbonized polymer dots (CPDs) targeting Aβ aggregation is reported. CPDs inhibit the fibrillization of Aβ monomers and rapidly disintegrate Aβ fibrils by electrostatic interactions, hydrogen‐bonding and hydrophobic interactions with Aβ in a time scale of seconds to minutes. Moreover, the interactions make CPDs label Aβ fibrils and emit enhanced red fluorescence by the binding, so CPDs can be used for in vivo imaging of the amyloids in transgenic Caenorhabditis elegans CL2006 as an AD model. Importantly, CPDs are demonstrated to scavenge the in vivo amyloid plaques and to promote the lifespan extension of CL2006 strain by alleviating the Aβ‐triggered toxicity. Taken together, the multifunctional CPDs show an exciting prospect for further investigations in Aβ‐targeted AD treatment and diagnosis, and this study provides new insight into the development of carbon materials in AD theranostics.

β-Amyloid (Aβ) fibrillogenesis is closely associated with the pathogenesis of Alzheimer’s disease (AD), so detection and inhibition of Aβ 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 Aβ 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 Aβ aggregates, especially for soluble Aβ oligomers. CHG NPs displayed weak emission in the monodispersed state, while they remarkably emitted increased red fluorescence upon interacting with Aβ 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 Aβ aggregation, the Aβ 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 Aβ aggregates via various electronic conjugations and hydrogen bonding, electrostatic, and hydrophobic interactions. Besides fluorescent imaging/probing, CHG NPs over 360 μg/mL could almost completely inhibit the formation of Aβ fibrils, exhibiting the capability of regulating Aβ aggregation. In-vivo assays with Caenorhabditis elegans CL2006 demonstrated the potency of CHG NPs as an effective theranostic nanoagent for imaging Aβ plaques and inhibiting Aβ deposition. The findings proved the potential of CHG NPs for development as a potent agent for the diagnosis and treatment of AD.

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