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.

酶自催化可以导致反馈反应，从而可以开发化学开关，切换器和振荡器。这些系统的非线性响应在响应式软材料中具有潜在的应用在开发医疗技术中。我们的目标是通过（i）趋化性（i）趋化性（i）趋化（i）趋化囊泡（朝着高浓度的底物运动）和（ii）触发疗法化合物的释放。该项目将限制基于囊泡的“人造细胞器”管腔内的自催化酶反应。这些人造细胞器将对存在的酶的存在有非线性响应，从而产生了一种生化开关，该开关激活了系统性能的理想变化。首先，我们将在其底物和底物浓度梯度的存在下表征和理解这些囊泡的运动。这种理解将使可以在复杂媒体中游泳的粒子的发展。其次，我们将开发出对代谢产物响应的受控释放的系统，并在实验药物输送模型系统中证明了这一应用。这将使触发的治疗化合物在目标位置释放或在本地环境中发生预期的变化。该项目将开始封装囊泡内部良好的自身催化性尿素 - 尿液反应，但随后将扩大以研究其他自体催化代谢物 - 酶 - 酶 - 酶 - 酶 - 酶 - 酶结合。最终，这项研究将旨在开发一种普遍的方法来创建具有人工细胞和纳米医学中应用的代谢物触发囊泡。