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用于治疗阿尔茨海默病的神经诊疗学中的量子点

Quantum dots in neurotheranostics for the treatment of Alzheimer's disease.

作者信息

Sharma Tripti, Bashir Bushra, Sharma Prince, Andotra Nandani, Singh Sachin Kumar, Singh Thakur Gurjeet, Vishwas Sukriti

机构信息

School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar, Punjab 144411, India.

School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar, Punjab 144411, India; Sunway Biofunctional Molecules Discovery Centre (SBMDC), School of Medical and Life Sciences, Sunway University, Bandar Sunway 47500, Malaysia.

出版信息

Ageing Res Rev. 2025 Dec;112:102876. doi: 10.1016/j.arr.2025.102876. Epub 2025 Aug 20.

DOI:10.1016/j.arr.2025.102876
PMID:40846207
Abstract

Age-related neurodegeneration is one of the primary causes associated with the pathogenesis of Alzheimer's disease (AD). Currently, there are 5.8 million cases of AD worldwide. With the advancement in technology, the paradigm of treating the disease has shifted from one treatment or diagnosis to simultaneously diagnosing as well as treating the disease. Excellent efforts have been made by the scientists towards the development of nanotheranostics. Among them, quantum dots (QDs) have shown promising results due to their nanometer size, which enables them to cross the blood-brain barrier (BBB) and optical properties which help in imaging the environment/pathology inside the brain. Furthermore, their functionalization with the specific biomolecules or coupling with aptamers/proteins/peptides/antibodies offers site-specific detection of pathological biomarkers. The long-lasting, tunable, and strong fluorescence generated by them within the body helps in the selective detection of biomarkers at very low concentrations. This helps in the accurate and early diagnosis of AD. Their multiplexed sensing of multiple markers at a time due to the tunable property of their emission wavelengths, makes it a more specific and sensitive tool over microarray or other assays. Additionally, real-time tracking of drug delivery and parallel treatment of the disease at the targeted site make them a unique theranostic tool over other techniques. This review consolidates recent advances in QDs-based approaches, encompassing their physicochemical properties, blood-brain barrier (BBB) penetration strategies, synthesis, and functionalization techniques. The roles in targeted drug delivery, bioimaging, and biomarker detection, as well as their intrinsic therapeutic actions, including inhibition of amyloid beta formation and tau aggregation, antioxidative effects, and neuroprotection, have also been discussed. Multiple preclinical studies demonstrate the ability of QDs to enhance drug stability, improve BBB transport, enable high-sensitivity imaging of AD biomarkers, and modulate neuroinflammatory responses.

摘要

与年龄相关的神经退行性变是阿尔茨海默病(AD)发病机制的主要相关原因之一。目前,全球有580万例AD病例。随着技术的进步,治疗该疾病的模式已从单一治疗或诊断转变为同时进行诊断和治疗。科学家们在纳米诊疗技术的开发方面付出了巨大努力。其中,量子点(QDs)因其纳米尺寸显示出了有前景的结果,这使其能够穿过血脑屏障(BBB),并且其光学特性有助于对脑内环境/病理进行成像。此外,它们与特定生物分子的功能化或与适配体/蛋白质/肽/抗体的偶联可实现对病理生物标志物的位点特异性检测。它们在体内产生的持久、可调谐且强的荧光有助于在极低浓度下选择性检测生物标志物。这有助于AD的准确早期诊断。由于其发射波长的可调谐特性,它们能够同时对多个标志物进行多重传感,使其成为比微阵列或其他检测方法更具特异性和敏感性的工具。此外,对药物递送的实时跟踪以及在靶位点对疾病的并行治疗使它们成为优于其他技术的独特诊疗工具。本综述总结了基于量子点方法的最新进展,包括其物理化学性质、血脑屏障(BBB)穿透策略、合成及功能化技术。还讨论了它们在靶向药物递送、生物成像和生物标志物检测中的作用,以及它们的内在治疗作用,包括抑制淀粉样β蛋白形成和tau蛋白聚集、抗氧化作用和神经保护作用。多项临床前研究证明了量子点增强药物稳定性、改善血脑屏障转运、实现AD生物标志物高灵敏度成像以及调节神经炎症反应的能力。

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