Nitrogen‐Doped Carbonized Polymer Dots: A Potent Scavenger and Detector Targeting Alzheimer's β‐Amyloid Plaques

Abstract

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.

Inorganic Nanomaterial for Biomedical Imaging of Brain Diseases

“…As shown in Figure 2 a, the green fluorescence signal of ThT-labeled Aβ40 aggregates decreased with the increase in the concentration of CPDs, which was due to the inhibitory effect of CPDs. Additionally, the interaction between CPDs and Aβ40 aggregates resulted in different red fluorescent plaques [ 84 ]. In addition to the application of carbon-based nanomaterials in the diagnosis and treatment of AD, they also have great potential in revealing the detailed functions and pathophysiology of the living brain.…”

“… ( a ) FL of Aβ40 incubated with or without CPDs after 56 h at 37 °C, reprinted from [ 84 ]. Copyright 2020, with permission from Weily; ( b ) MRS spectra of subcutaneously transplanted glioma before and after the intratumoral injection of 1 mL AMSNs physiological saline solution (10 mg AMSNs/mL, 40 mg AMSNs/kg), reprinted from [ 77 ].…”

Nanomaterials for Modulating the Aggregation of β-Amyloid Peptides

“…Among them, CDs with red fluorescence possess several advantages of low biological fluorescence background signal and high tissue penetration ability. Recently, Gao et al discovered new functions of nitrogen-doped carbonized polymer dots (CPDs) to target Aβ aggregation [ 101 ]. The non-covalent interactions between Aβ aggregates and CPDs limited the molecular vibration and rotation of CPDs, resulting in the red emission.…”

“…(b) Fluorescent images of inhibiting Aβ deposits after treating without (b1,b2) or with (b3,b4) CPDs in CL2006 nematodes. Reprinted with permission from reference [ 101 ]. Copyright 2020 Wiley-VCH.…”

Mechanisms Involved in Microglial-Interceded Alzheimer’s Disease and Nanocarrier-Based Treatment Approaches

“…Recently, ceramide nanomicelles and curcumin were studied. The use of these nanomicelles degraded the tau protein and induced autophagy that cumulatively resulted in an anti-Alzheimer's effect [156].…”