槲皮素衍生的红色发射碳点:一种多功能治疗性纳米探针,用于对抗阿尔茨海默病β-淀粉样纤维形成。

Quercetin-derived red emission carbon dots: A multifunctional theranostic nano-agent against Alzheimer's β-amyloid fibrillogenesis.

机构信息

Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China.

Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China.

出版信息

Colloids Surf B Biointerfaces. 2024 Jun;238:113907. doi: 10.1016/j.colsurfb.2024.113907. Epub 2024 Apr 9.

Abstract

Multifunctional agents with therapeutic and diagnostic capabilities are imperative to the prevention of Alzheimer's disease (AD), which is considered due to abnormal aggregation and deposition of β-amyloid protein (Aβ) as well as oxidative stress. Herein, quercetin (Que)- and p-phenylenediamine (p-PD)-derived red emission carbon dots (CDs) synthesized via a one-step hydrothermal method were designed as a novel theranostic nano-agent for the multi-target treatment of AD. R-CD-75 with an optimized composition exhibited significant inhibition of Aβ aggregation and rapid depolymerization of mature Aβ fibrils (<4 h) at micromolar concentrations (2 and 5 μg/mL, respectively). Moreover, R-CD-75 potently scavenged reactive oxygen species and showed turned-on red fluorescence imaging of Aβ plaques both in vitro and in vivo. In vitro assays proved that R-CD-75 significantly mitigated the Aβ-induced cytotoxicity and enhanced the cultured cell viability from 74.9 % to 98.0 %, while in vivo studies demonstrated that R-CD-75 prolonged the lifespan of AD nematodes by over 50 % (from 13 to 20 d). Compared to the precursors Que and p-PD, R-CD-75 inherited some of their structures and functional groups, such as aromatic structures, phenolic hydroxyl and amino groups, which were considered to interact with Aβ species through hydrogen bonding, electrostatic interactions, hydrophobic interactions, and π-π stacking, thus contributing to its effectiveness in its theranostic functions. This research has opened a new avenue to the development of potent theranostic agents by designing novel carbon dots.

摘要

多功能试剂兼具治疗和诊断功能,对于阿尔茨海默病(AD)的预防至关重要。AD 被认为是由于β-淀粉样蛋白(Aβ)的异常聚集和沉积以及氧化应激引起的。在此,通过一步水热法合成了槲皮素(Que)和对苯二胺(p-PD)衍生的红色发射碳点(CDs),作为一种新型的治疗学纳米试剂,用于 AD 的多靶点治疗。具有最佳组成的 R-CD-75 在微摩尔浓度(分别为 2 和 5μg/mL)下,对 Aβ聚集具有显著的抑制作用,并能迅速解聚成熟的 Aβ纤维(<4h)。此外,R-CD-75 能有效清除活性氧,并能在体外和体内对 Aβ斑块进行开启式红色荧光成像。体外实验证明,R-CD-75 能显著减轻 Aβ诱导的细胞毒性,使培养细胞的存活率从 74.9%提高到 98.0%,而体内研究表明,R-CD-75 能使 AD 线虫的寿命延长 50%以上(从 13 天延长到 20 天)。与前体 Que 和 p-PD 相比,R-CD-75 继承了它们的一些结构和官能团,如芳香结构、酚羟基和氨基,这些结构和官能团被认为通过氢键、静电相互作用、疏水相互作用和π-π堆积与 Aβ相互作用,从而有助于其在治疗学功能中的有效性。这项研究通过设计新型碳点,为开发有效的治疗学试剂开辟了新途径。

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