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Engineering a nanoscale liposome-in-liposome for in situ biochemical synthesis and multi-stage release
Nature Chemistry ( IF 19.2 ) Pub Date : 2024-07-15 , DOI: 10.1038/s41557-024-01584-z
Colin P Pilkington 1, 2 , Ignacio Gispert 2 , Suet Y Chui 2 , John M Seddon 1 , Yuval Elani 2
Affiliation  

Soft-matter nanoscale assemblies such as liposomes and lipid nanoparticles have the potential to deliver and release multiple cargos in an externally stimulated and site-specific manner. Such assemblies are currently structurally simplistic, comprising spherical capsules or lipid clusters. Given that form and function are intertwined, this lack of architectural complexity restricts the development of more sophisticated properties. To address this, we have devised an engineering strategy combining microfluidics and conjugation chemistry to synthesize nanosized liposomes with two discrete compartments, one within another, which we term concentrisomes. We can control the composition of each bilayer and tune both particle size and the dimensions between inner and outer membranes. We can specify the identity of encapsulated cargo within each compartment, and the biophysical features of inner and outer bilayers, allowing us to imbue each bilayer with different stimuli-responsive properties. We use these particles for multi-stage release of two payloads at defined time points, and as attolitre reactors for triggered in situ biochemical synthesis.



中文翻译:


设计纳米级脂质体包脂质体,用于原位生化合成和多阶段释放



软物质纳米级组件(例如脂质体和脂质纳米颗粒)具有以外部刺激和特定位点方式递送和释放多种货物的潜力。目前,此类组件的结构比较简单,包括球形胶囊或脂质簇。鉴于形式和功能是交织在一起的,建筑复杂性的缺乏限制了更复杂属性的开发。为了解决这个问题,我们设计了一种结合微流体和缀合化学的工程策略,合成具有两个离散隔室的纳米脂质体,一个隔室位于另一个隔室中,我们将其称为集中体。我们可以控制每个双层的组成并调整颗粒大小以及内膜和外膜之间的尺寸。我们可以指定每个隔室内封装的货物的身份,以及内部和外部双层的生物物理特征,使我们能够为每个双层注入不同的刺激响应特性。我们使用这些颗粒在规定的时间点多阶段释放两个有效载荷,并作为阿托升反应器来触发原位生化合成。

更新日期:2024-07-15
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