The design of high-efficiency scavengers targeting β-amyloid protein (Aβ) plaques in the progress of Alzheimer's disease (AD) has been recognized as an effective way to prevent and treat AD. Herein, epigallocatechin gallate (EGCG)-derived carbonized polymer dots (E-CPDs) were synthesized for the first time via a hydrothermal method using EGCG, an Aβ inhibitor, as one of the raw materials. The inhibitory efficiency and fluorescent property of E-CPDs were elegantly modulated by adjusting the molar ratio of EGCG to nitrogen-containing dopant, o-phenylenediamine (oPD), and 75E-CPDs fabricated with 75 mM EGCG and 50 mM oPD showed the highest inhibitory capability. The multifunctionality of 75E-CPDs on inhibition of Aβ fibrillization, Aβ fibrils disaggregation, amyloid fluorescent detection, and intracellular reactive oxygen species scavenging was demonstrated. 75E-CPDs inhibited the formation of β-sheet-rich Aβ aggregates, alleviated Aβ-induced cytotoxicity of cultured cells from 47% to 15%, and prolonged the lifespan of AD nematodes by scavenging in vivo amyloid plaques, demonstrating much higher performance than either EGCG or EGCG-free carbon dots. Notably, 75E-CPDs could rapidly disaggregate Aβ fibrils on "second" scale, faster than any other disaggregating agents. The aromatic structure as well as hydroxyl and carboxyl groups existing on 75E-CPDs surface, which would interact with Aβ species via hydrogen bonding, electrostatic interactions, and hydrophobic interactions, played critical roles in their inhibition and disaggregation capabilities. This work reveals that potent CDs can be fabricated by using an Aβ inhibitor as the precursor, providing a new perspective for the design of multifunctional scavengers targeting amyloid plaques. STATEMENT OF SIGNIFICANCE: Alzheimer's disease (AD) is one of the top ten causes of death worldwide and seriously threatens human health. Recently, carbon nanomaterials have attracted much attention because of their good biocompatibility and capability in modulating Aβ aggregation via multiple interactions. This work has for the first time fabricated epigallocatechin gallate-derived carbonized polymer dots (E-CPDs) and revealed the multifunctional potency of E-CPDs on alleviating the multifaced symptoms associated with β-amyloid protein (Aβ) fibrillization in the progression of AD. Notably, E-CPDs exhibited enhanced fluorescence emission upon binding to Aβ fibrils, possessing potential as Aβ fluorescent probes. It is believed that this work would open a new horizon in the design of multifunctional carbon nanomaterials as a potent amyloid scavenger for AD theranostics.
Keywords: Alzheimer's disease; Carbon dots; Epigallocatechin gallate (EGCG); Multifunctionality; Scavenger; β-amyloid protein.
Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.