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树状大分子架构在癌症和神经退行性疾病治疗中的应用及其在治疗诊断学和个性化医学中的意义。

Dendrimer Architectonics to Treat Cancer and Neurodegenerative Diseases with Implications in Theranostics and Personalized Medicine.

机构信息

Bioorganic Chemistry Laboratory, New Chemistry Unit and The School of Advanced Materials (SAMat), Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur P. O., Bengaluru, Karnataka 560064, India.

出版信息

ACS Appl Bio Mater. 2021 Feb 15;4(2):1115-1139. doi: 10.1021/acsabm.0c01319. Epub 2021 Jan 13.

Abstract

Integration of diagnostic and therapeutic functions in a single platform namely theranostics has become a cornerstone for personalized medicine. Theranostics platform facilitates noninvasive detection and treatment while allowing the monitoring of disease progression and therapeutic efficacy in case of chronic conditions of cancer and Alzheimer's disease (AD). Theranostic tools function by themselves or with the aid of carrier, liposomes, micelles, polymers, or dendrimers. The dendrimer architectures (DA) are well-characterized molecular nanoobjects with a large number of terminal functional groups to enhance solubility and offer multivalency and multifunctional properties. Various noninvasive diagnostic tools like magnetic resonance imaging (MRI), computed tomography (CT), gamma scintigraphy, and optical techniques have been accomplished utilizing DAs for simultaneous imaging and drug delivery. Obstacles in the formulation design, drug loading, payload delivery, biocompatibility, overcoming cellular membrane and blood-brain barrier (BBB), and systemic circulation remain a bottleneck in translational efforts. This review focuses on the diagnostic, therapeutic and theranostic potential of DA-based nanocarriers in treating cancer and neurodegenerative disorders like AD and Parkinson's disease (PD), among others. In view of the inverse relationship between cancer and AD, designing suitable DA-based theranostic nanodrug with high selectivity has tremendous implications in personalized medicine to treat cancer and neurodegenerative disorders.

摘要

将诊断和治疗功能集成在一个平台上,即治疗学,已成为个性化医疗的基石。治疗学平台促进了非侵入性的检测和治疗,同时允许在癌症和阿尔茨海默病(AD)等慢性疾病的情况下监测疾病进展和治疗效果。治疗工具可以单独使用,也可以借助载体(如脂质体、胶束、聚合物或树枝状大分子)使用。树状大分子(DA)是具有大量末端官能团的结构明确的分子纳米物体,可提高溶解度,并提供多价和多功能特性。已经利用各种非侵入性诊断工具,如磁共振成像(MRI)、计算机断层扫描(CT)、伽马闪烁成像和光学技术,实现了同时成像和药物输送的目的。在制剂设计、药物负载、有效载荷输送、生物相容性、克服细胞膜和血脑屏障(BBB)以及全身循环方面的障碍仍然是转化研究的瓶颈。本综述重点介绍了基于 DA 的纳米载体在治疗癌症和神经退行性疾病(如 AD 和帕金森病(PD))方面的诊断、治疗和治疗学潜力。鉴于癌症和 AD 之间存在反比关系,设计具有高选择性的合适的基于 DA 的治疗学纳米药物对个性化医学治疗癌症和神经退行性疾病具有重要意义。

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