Artificial organelles encapsulating autocatalytic enzyme reactions for application in controlled release and chemotactic transport

封装自催化酶反应的人工细胞器用于控制释放和趋化运输

• 批准号: 2593867
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2593867
• 关键词: Artificial; organelles; encapsulating; autocatalytic; enzyme

Enzyme autocatalysis can lead to a feedback response that allows the development of chemical switches, toggles and oscillators. The non-linear response of these systems have potential applications in responsive soft materials for developing healthcare technologies.We will aim to develop responsive vesicles that respond to metabolites in their environment by (i) chemotaxis (active motion towards or away from high concentrations of substrate), and (ii) triggered release of therapeutic compounds. This project will confine autocatalytic enzyme reactions inside the lumen of vesicle-based "artificial organelles". These artificial organelles will have a non-linear response to the presence of the confined enzyme, producing a biochemical switch that activates a desirable change in system properties. Firstly, we will characterise and understand the motility of these vesicles in the presence of their substrate and in substrate concentration gradients. This understanding will enable the development of particles that can swim to target locations within complex media. Secondly, we will develop systems that exhibit controlled release in response to a metabolite and demonstrate this application in experimental drug delivery model systems. This will enable the triggered release of therapeutic compounds at a target location or with a desired change in the local environment.The project will begin with encapsulating the well-studied autocatalytic urea-urease reactions inside vesicles but will then broaden to study other autocatalytic metabolite-enzyme combinations. Ultimately this research will aim to develop a generalised approach to creating metabolite-triggered vesicles with applications in artificial cells and nanomedicines.

酶的自催化作用可以产生反馈反应，从而促进化学开关、切换和振荡器的发展。这些系统的非线性响应在用于开发医疗保健技术的响应性软材料中具有潜在的应用。我们的目标是开发响应性囊泡，通过（i）趋化性（朝向或远离高浓度底物的主动运动）对其环境中的代谢物做出反应），以及（ii）触发治疗化合物的释放。该项目将把自催化酶反应限制在基于囊泡的“人工细胞器”的内腔内。这些人工细胞器将对受限酶的存在产生非线性响应，产生生化开关，激活系统特性的所需变化。首先，我们将表征并了解这些囊泡在底物存在和底物浓度梯度下的运动性。这种理解将使粒子能够游动到复杂介质中的目标位置。其次，我们将开发响应代谢物而表现出受控释放的系统，并在实验药物输送模型系统中展示这种应用。这将使治疗化合物在目标位置或局部环境发生所需变化时触发释放。该项目将从将经过充分研究的自催化尿素-脲酶反应封装在囊泡内开始，但随后将扩大到研究其他自催化代谢物-酶组合。最终，这项研究的目标是开发一种通用方法来创建代谢物触发的囊泡，并应用于人造细胞和纳米医学。