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有机体的结构和行为，这些分子模拟生物学中存在的结构，功能和信息。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应对周围的世界。随着我们构建能够模仿这些行为的越来越复杂的合成细胞，我们还创造了可应用于社会挑战的工具，例如医学治疗和有用化学品的生产。最近，我们已经展示了一种合成细胞（SynCell）技术，该技术可以在其局部环境中检测蛋白质生物分子的特定组合，并作为响应释放分子货物。这种行为在与蛋白质水平增加相关的疾病（如多种类型的癌症）的药物递送中具有潜在的应用。在这个项目中，我们提出了一个可行性研究的SynCells，可以响应前列腺癌肿瘤作为一个新的输送系统，用于治疗晚期，耐药前列腺癌。该路线图涉及修改SynCell结构以增加其在人体内的稳健性，将SynCell靶向肿瘤，开发不同的SynCell释放行为，并测试SynCell在体内循环并被前列腺吸收的能力。该项目将使新的药物递送载体的验证能够克服当前方法的重大局限性，它们不具备感知生物环境的能力。这些运载工具可以使新的治疗方法被开发用于前列腺癌，以及其他生物化学类似的癌症，如乳腺癌，卵巢癌和胰腺癌。此外，如果在这里开发的合成细胞材料被证明是有效的输送系统，这可以作为开发许多合成细胞技术的第一步，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.