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

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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.