Re-Engineering Extracellular Vesicles as Smart Nanoscale Therapeutics.

Re-Engineering Extracellular Vesicles as Smart Nanoscale Therapeutics.
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DOI:
10.1021/acsnano.6b07607
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发表时间:
2017-01-24
期刊:
影响因子:
17.1
通讯作者:
Stevens MM
Stevens MM
中科院分区:
材料科学1区
文献类型:
--
作者:
Armstrong JP;Holme MN;Stevens MM

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在过去的十年里,细胞外小泡(EVS)已经成为一种关键的无细胞策略,用于治疗一系列病理疾病,包括癌症、心肌梗死和炎症性疾病。事实上,该领域正在从有希望的体外报告迅速过渡到体内动物模型和早期临床研究。这些研究利用了EVS的高物理化学稳定性和生物相容性,以及它们通过信号转导和膜融合与细胞进行远距离通信的固有能力。本综述将集中于对EVS进行化学或生物修饰以扩大、改变或增强其治疗能力的方法。我们将考察两种广泛的策略,这两种策略已被用于引入广泛的纳米颗粒、报告系统、靶向肽、药剂学和功能RNA分子。首先,我们将探索如何通过操纵母体细胞来修饰电动汽车;无论是通过基因工程或代谢工程,还是通过引入外源物质,然后将其整合到分泌的电动汽车中。其次,我们考虑如何使用疏水插入、共价表面化学和膜通透性等策略将EVS直接功能化。我们将讨论每项具体技术的历史背景,提供突出的例子,并评估不同的再工程战略带来的复杂性、潜在陷阱和机会。
In the last decade, extracellular vesicles (EVs) have emerged as a key cell-free strategy for the treatment of a range of pathologies, including cancer, myocardial infarction and inflammatory diseases. Indeed, the field is rapidly transitioning from promising in vitro reports towards in vivo animal models and early clinical studies. These investigations exploit the high physicochemical stability and biocompatibility of EVs, as well as their innate capacity to communicate with cells over long distances via signal transduction and membrane fusion. This review will focus on methods in which EVs can be chemically or biologically modified to broaden, alter or enhance their therapeutic capability. We will examine two broad strategies, which have been used to introduce a wide range of nanoparticles, reporter systems, targeting peptides, pharmaceutics and functional RNA molecules. First, we will explore how EVs can be modified by manipulating their parent cells; either through genetic or metabolic engineering, or by introducing exogenous material that is subsequently incorporated into secreted EVs. Second, we consider how EVs can be directly functionalized using strategies such as hydrophobic insertion, covalent surface chemistry and membrane permeabilization. We will discuss the historical context of each specific technology, present prominent examples and evaluate the complexities, potential pitfalls and opportunities presented by different re-engineering strategies.
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