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多功能纳米载体用于血脑屏障的诊断、药物输送和靶向治疗:追踪和神经影像学的观点。

Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging.

机构信息

Comprehensive Pneumology Centre, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Neuherberg, Germany.

出版信息

Part Fibre Toxicol. 2010 Mar 3;7:3. doi: 10.1186/1743-8977-7-3.

DOI:10.1186/1743-8977-7-3
PMID:20199661
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2847536/
Abstract

Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered.

摘要

纳米技术为生物发现和临床实践带来了各种新的可能性。特别是,纳米级载体使药物输送发生了革命性变化,使治疗剂能够在器官、组织和细胞特异性水平上进行选择性靶向,同时使健康组织对药物的暴露最小化。在这篇综述中,我们讨论和分析了三个被认为是纳米级药物输送系统核心的问题,即纳米载体的功能化、靶向器官的输送和体内成像。首先回顾了用于将生物分子附着到纳米颗粒(NP)表面的高度特异性偶联策略的最新进展。除了药物携带能力外,纳米载体的功能化还有助于它们向主要靶器官运输。我们强调了纳米载体的主要优势,即它们能够穿过血脑屏障(BBB),BBB 是围绕大脑的一层紧密排列的内皮细胞,阻止高分子量分子进入大脑。BBB 有几个转运分子,如生长因子、胰岛素和转铁蛋白,它们可以潜在地提高脑靶向纳米载体的效率和动力学。因此,针对中风、肿瘤和阿尔茨海默病等常见神经疾病的治疗是纳米医学的一个非常受欢迎的应用。同样,对于任何其他药物输送系统,一旦给予功能化 NPs,就需要登记许多参数,例如它们在器官选择性靶向、生物积累和排泄方面的效率。最后,纳米材料的直接体内成像为那些纳米载体提供了实时跟踪的机会,是一个令人兴奋的新兴领域。我们综述了一系列适用于体内成像和药物输送监测的系统,重点介绍了最近引入的基于光学和混合对比的分子成像模态,如荧光蛋白断层扫描和多光谱光声断层扫描。总的来说,纳米载体在医学诊断、治疗和分子靶向方面具有巨大的潜力。因此,详细讨论了正在进行和未来的研究方向的建议路线图,重点是开发用于功能化、靶向和成像纳米药物输送系统的新方法,这是一项改变医学给药方式的前沿技术。

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