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Magnetic nanofactories: localized synthesis and delivery of quorum-sensing signaling molecule autoinducer-2 to bacterial cell surfaces.

机译:磁性纳米工厂:群体感应信号分子autoinducer-2的局部合成和传递到细菌细胞表面。

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摘要

Magnetic 'nanofactories', for localized manufacture and signal-guided delivery of small molecules to targeted cell surfaces, are demonstrated. They recruit nearby raw materials for synthesis, employ magnetic mobility for capture and localization of target cells, and deliver molecules to cells triggering their native phenotypic response, but with user-specified control. Our nanofactories, which synthesize and deliver the "universal" bacterial quorum-sensing signal molecule, autoinducer AI-2, to the surface of Escherichia coli, are assembled by first co-precipitating nanoparticles of iron salts and the biopolymer chitosan. E. coli AI-2 synthases, Pfs and LuxS, constructed with enzymatically activatable "pro-tags", are then covalently tethered onto the chitosan. These enzymes synthesize AI-2 from metabolite S-adenosylhomocysteine. Chitosan serves as a molecular scaffold and provides cell capture ability; magnetite provides stimuli responsiveness. These magnetic nanofactories are shown to modulate the natural progression of quorum-sensing activity. New prospects for small molecule delivery, based on localized synthesis, are envisioned.
机译:展示了磁性“纳米工厂”,可用于小分子的局部制造和信号引导下递送至目标细胞表面。他们收集附近的原料进行合成,利用磁迁移率捕获和定位靶细胞,然后将分子传递到触发其天然表型反应的细胞,但需要用户指定的控制权。我们的纳米工厂通过首先共沉淀铁盐和生物聚合物壳聚糖的纳米颗粒来组装,这些纳米工厂将“通用”细菌群体感应信号分子自动诱导物AI-2合成并传递到大肠杆菌表面。然后将可酶活化的“前标签”构建的大肠杆菌AI-2合酶,Pfs和LuxS共价束缚在壳聚糖上。这些酶从代谢物S-腺苷同型半胱氨酸合成AI-2。壳聚糖充当分子支架并提供细胞捕获能力。磁铁矿提供刺激反应。这些磁性纳米工厂显示出可以调节群体感应活动的自然进程。展望了基于局部合成的小分子递送的新前景。

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