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

酶的自动催化作用可以导致反馈反应，从而允许化学开关，触发器和振荡器的发展。这些系统的非线性响应在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，其通过（i）趋化性（朝向或远离高浓度底物的主动运动）和（ii）触发释放治疗化合物来响应环境中的代谢物。该项目将限制自催化酶反应在基于囊泡的“人造细胞器”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，产生生物化学开关，激活系统特性的期望变化。首先，我们将研究和了解这些囊泡在底物存在下和底物浓度梯度下的运动性。这种理解将使粒子的发展，可以游泳到复杂介质中的目标位置。其次，我们将开发系统，表现出控制释放的代谢产物，并证明这种应用在实验药物输送模型系统。该项目将开始将研究充分的自催化尿素-尿素酶反应封装在囊泡内，然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的方法来创建代谢物触发的囊泡，并应用于人工细胞和纳米医学。

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.