21ENGBIO: Microenvironment-Responsive Synthetic Cells for Cancer Drug Delivery

自下而上的合成生物学旨在通过分子的自组装来复制细胞生物的结构和行为，这些分子模仿了生物学中存在的结构、功能和包含信息的角色。这些结构被称为合成细胞，它们可以作为研究生物过程（如运动或复制）的框架。细胞能够同时承担许多任务，并且已经进化到改变它们的行为以响应周围的世界。当我们构建越来越复杂的合成细胞来模仿这些行为时，我们也创造了可以应用于社会挑战的工具，比如医疗疗法和有用化学物质的生产。最近，我们展示了一种合成细胞（SynCell）技术，它可以感知局部环境中蛋白质生物分子的特定组合，并相应地释放分子货物。这种行为在治疗与蛋白质水平升高有关的疾病（如多种类型的癌症）的药物输送中具有潜在的应用价值。在这个项目中，我们提出了一项可行性研究，SynCells可以对前列腺癌肿瘤作出反应，作为治疗晚期耐药前列腺癌的新递送系统。该路线图包括修改SynCell结构以增加其在人体中的稳健性，将SynCell靶向肿瘤，开发不同的SynCell释放行为，并测试SynCell在身体周围循环并被前列腺吸收的能力。该项目将验证一种新的药物输送载体，该载体可以克服当前方法的重大限制，这些方法不具备感知其生物环境的能力。这些运载工具可以为前列腺癌以及其他生物化学上类似的癌症，如乳腺癌、卵巢癌和胰腺癌，开发新的治疗方法。此外，如果在这里开发的合成细胞材料被证明是有效的传递系统，这可以作为许多合成细胞技术发展的第一步，这些技术可以应用于生物医学的其他方面，如诊断。

Bottom-up synthetic biology aims to reproduce the structures and behaviours of cellular organisms through the self-assembly of molecules that mimic the structural, functional and information containing roles present in biology. These structures are known as synthetic cells, and they can act as a framework to study biological processes (such as movement or replication). Cells are able to undertake many tasks at once and have evolved to change their behaviours in response to the world around them. As we build increasingly complex synthetic cells that can mimic these behaviours, we also create tools that can be applied to societal challenges such as medical therapies and the production of useful chemicals. Recently, we have demonstrated a synthetic cell (SynCell) technology that can sense specific combinations of protein biomolecules in their local environment, and in response release a molecular cargo. This behaviour has potential applications in the delivery of drugs for diseases that are associated with increased protein levels, such as multiple types of cancer. In this project we propose a feasibility study of SynCells that can respond to prostate cancer tumours as a new delivery system for the treatment of advanced, drug resistant prostate cancer. This roadmap involves modifying the SynCell structure to increase its robustness in the human body, targeting the SynCells to tumours, developing different SynCell release behaviours and testing the ability of SynCells to circulate around the body and be taken up by the prostate.This project will enable the validation of a new drug delivery vehicle that could overcome a significant limitation of current methods, which do not possess the ability to sense their biological environment. These delivery vehicles could enable new treatments to be developed for prostate cancer, as well as other biochemically similar cancers such as breast, ovarian and pancreatic cancer. Furthermore, if the synthetic cell materials developed here are shown to be effective delivery systems, this could act as the first step for the development of many synthetic cell technologies that could be applied in other aspects of biomedicine such as diagnostics.