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Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing

机译:趋化性合成囊泡:在血脑屏障穿越中的设计和应用

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摘要

In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano- or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro- and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor–related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems.
机译:近年来,科学家已经创造出了能够模仿生物运动和滑行的人造的微观和纳米自推进颗粒,通常被称为纳米或微游泳器。这种主动扩散使工程设计复杂的操作成为可能,而到目前为止,这在微米和纳米规模上是不可能的。最有前途的任务之一是工程化纳米载体的能力,这些载体可以在组织和器官内自主导航,在内源性化学梯度的引导下进入人体的几乎每个部位。我们报告了一种完全合成的有机纳米系统,它表现出由葡萄糖的酶促转化驱动的有吸引力的趋化性。我们通过将葡萄糖氧化酶单独或与过氧化氢酶组合封装入纳米级和生物相容性不对称聚合物囊泡(称为多聚体)中来实现。我们显示这些囊泡通过在其表面上引起滑移速度而响应于葡萄糖的外部梯度而自我推进,这使它们以极其敏感的方式向较高浓度区域移动。我们最终证明,与非化学趋化系统相比,这些纳米游泳剂的化学趋化行为与LRP-1(低密度脂蛋白受体相关蛋白1)的靶向作用相结合,可使对脑部的渗透增加四倍。

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