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

酶的自动催化作用可以产生反馈反应，从而形成化学开关、开关和振荡器。这些系统的非线性响应在开发医疗保健技术的响应软材料方面具有潜在的应用。我们的目标是开发响应囊泡，通过(I)趋化性(向或远离高浓度底物的主动运动)和(Ii)触发治疗化合物的释放来响应环境中的代谢物。这个项目将限制以囊泡为基础的“人造细胞器”管腔内的自催化酶反应。这些人造细胞器将对受限酶的存在产生非线性反应，产生一种生化开关，激活系统属性的理想变化。首先，我们将表征和了解这些囊泡在底物和底物浓度梯度存在时的运动性。这一认识将使粒子能够游到复杂介质中的目标位置。其次，我们将开发对代谢物进行控制释放的系统，并在实验药物输送模型系统中演示这一应用。这将使治疗性化合物在目标位置或在局部环境发生所需变化时被触发释放。该项目将首先将研究良好的自催化尿素-尿素酶反应封装在囊泡中，但随后将扩大到研究其他自催化代谢物-酶组合。最终，这项研究将致力于开发一种通用的方法来创建代谢物触发的囊泡，并将其应用于人造细胞和纳米医学。

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.