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用于神经退行性疾病的纳米诊疗剂。

Nanotheranostic agents for neurodegenerative diseases.

机构信息

Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Singapore 636921.

Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.

出版信息

Emerg Top Life Sci. 2020 Dec 17;4(6):645-675. doi: 10.1042/ETLS20190141.

Abstract

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

摘要

神经退行性疾病(NDDs),包括阿尔茨海默病(AD)和帕金森病(PD),影响着全球的老年人群体,不仅严重降低了数百万人的生活质量,还给人口逐渐老龄化的国家带来了巨大的经济负担。近年来,除了寻找用于早期检测和预测的生物标志物外,治疗方法的研究也变得越来越深入。已经探索了各种有前途的治疗方法,重点是早期预防和保护,包括但不限于基因治疗、干细胞治疗、免疫治疗和放射治疗。许多药物干预措施已被证明是有前途的新途径,但成功的应用常常受到治疗剂穿过血脑屏障(BBB)的输送不良的阻碍。为了克服这一挑战,纳米颗粒(NP)介导的药物输送被认为是一种很有前途的选择,因为基于 NP 的药物输送系统可以被功能化以靶向特定的细胞表面受体,并实现治疗剂对目标组织的控制和长期释放。NP 在装载和输送药物方面的用途在 NDD 背景下已经得到了广泛的研究,并且它们在许多临床前动物模型中的生物学功效已经得到了证明。还努力开发可以用于靶向 BBB 和大脑中各种细胞类型的 NP。本文的主要重点是简要讨论功能化 NP 作为诊断和治疗 NDD 的有前途的治疗剂的优势。我们还总结了专门研究不同 NP 用于治疗 NDD 的各种研究的结果,特别强调 AD 和 PD 以及相关的病理生理变化。最后,我们对将 NP 用作治疗剂的现有挑战以及改进它们的可能未来方法提供了一些观点。

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