Large Amino Acid Mimicking Selenium-Doped Carbon Quantum Dots for Multi-Target Therapy of Alzheimer’s Disease

Abstract

Multi-target intervention and synergistic treatment are critical for the drug development of Alzheimer’s disease (AD) due to its complex and multifactional nature. Oxidative stress and amyloid β peptides (Aβ) accumulation have been recognized as therapeutic targets for AD. Herein, with ability to inhibit Aβ aggregation and the broad-spectrum antioxidant properties, the large amino acid mimicking selenium-doped carbon quantum dots (SeCQDs) are presented as novel nanoagents for multi-target therapy of AD. Compared with the precursor, selenocystine, SeCQDs which maintain the intrinsic properties of both selenium and carbon quantum dots (CQDs) possess good biocompatibility and a remarkable ROS-scavenging activity. Moreover, the functionalized α-carboxyl and amino groups on edge of SeCQDs can trigger multivalent interactions with Aβ, leading to the ability of SeCQDs to inhibit Aβ aggregation. In vivo study demonstrated that SeCQDs can significantly ameliorate the Aβ induced memory deficits, reduce Aβ accumulation and inhibit neuron degeneration in AD model rats. The versatility of functionalization and potential ability to cross the blood-brain barrier (BBB) make SeCQDs as prospective nanodrugs for treating AD.

Advanced nanomaterials for modulating Alzheimer's related amyloid aggregation

“…Inhibiting Aβ aggregation and Scavenging the ROS [221] Se-CQDs Anti-oxidation Scavenging the ROS [222] gCDs-E Hydrophobic interactions/anti-oxidation Suppressing fibrillation/ Disaggregation/Inhibition fungi [13] bPEI@CDs Electrostatic interactions/ photooxygenation Inhibition/Disaggregation [231] OPCDs Chelation/hydrophobic interactions/ photooxygenation Inhibition [232] Apta@CDs Photooxygenation/target Inhibition [229] CPDs Electrostatic interactions/hydrogen bonds/hydrophobic interactions Inhibition/Disaggregation [233] C 60 Hydrophobic interactions Inhibition [234] UCNP@C 60 -pep Photooxygenation/anti-oxidation Inhibition/scavenging the ROS [236] 4 Others…”

“…This study contributed to understanding the pathological link between bacterial metabolites and amyloid diseases. Due to the excellent antioxidant capacity of selenium nanoparticles, Zhou et al 221 designed selenium-doped carbon quantum dots (Se-CQDs) via a simple hydrothermal treatment of selenocystine, which were successfully applied to inhibit Aβ aggregation and scavenge the redundant ROS in the brain ( Fig. 13B ).…”

“…CQDs were able to inhibit IAPP and Aβ aggregation induced by lipopolysaccharide (LPS) through hydrogen bonding and hydrophobic interactions. This study contributed to understanding the pathological link between bacterial metabolites and amyloid diseases.Due to the excellent antioxidant capacity of selenium nanoparticles, Zhou et al[221] designed selenium-doped carbon quantum dots (Se-CQDs) via a simple hydrothermal treatment of selenocystine, and were successfully applied to inhibit Aβ aggregation and scavenge the redundant ROS in the brain (Figure13 B). Se-CQDs maintained the intrinsic properties of both selenium and CQDs.…”

Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage

“…Nanozyme usually refers to artificial enzymes which present highly effective enzyme-like properties and could be widely used for anti-inflammatory, anti-oxidative damage and cancer treatments, etc. [23][24][25][26][27][28][29]. In recent years, studies have shown that cerium oxide nanoparticles (CNPs) present good antioxidant capacity and the ability to scavenge excess reactive oxygen species [30][31][32][33][34].…”

Design of carbon dots as nanozymes to mediate redox biological processes

“…More importantly, small-sized carbon dots can penetrate various biological barriers in the body providing therapeutic effects. 93,94 In addition to conventional imaging agents, CDs have developed many new applications as nanozymes in recent years, such as antibacterial mouthwash. 95 The various properties of CDs make promising for multi-functional diagnosis and treatment applications.…”