NanoDrill - A new versatile research tool - high spatial resolution light activated molecular nanomachines

点击翻译按钮获取中文摘要

An important need for future bio-medical and fundamental cell biology is the targeted in vivo destruction of selected cells and cell types. Cancer affects every country regardless of financial status, medical infrastructure or the availability of highly-skilled specialists and is responsible for 8.2 million deaths/year worldwide. Our vision for the future is to develop a series of light-activated molecular nanomachines - Nano-drills - to target cancerous cells selectively and safely eradicate them. Currently this can only be facilitated using highly invasive surgical or radiotherapeutic procedures that are often harmful to administer.We have already demonstrated that our Nano-drills (molecular Nano-Machines, MNMs) can selectively destroy cells using small quantities of ultraviolet activation light. The next phase of our research is four-fold. First, we must enable multi-two-photon (2PE) activation on our existing microscope system using biologically safe near-infra-red (NIR) light for live-cell studies. Second, extend the family of cell type and pathological condition specific nano-drills to allow a wide range of cancer cells to study. Third, design nano-drills that can be activated using plain visible light in order to comply with already established protocols in biomedical research. Fourth, create a new breed of nano-drills that will first be internalised by the targeted cancer cells and subsequently allowing eradication to be triggered them from within. This will promote a more controlled single-cell precision research tool.Preliminary studies showed that our MNMs can be successfully activated using 2PE. In order to continue this research, we need a fast, high resolution live cell capable Multi-Photon Microscope (MPM) to image live cells. Unfortunately, due to the nature and unique instrumental requirement an off the shelf MPM system costs in the region of £500,000. However, we propose to develop a suitable custom system by adapting existing equipment at fraction of the cost. We will equip our Leica SP5 II confocal system with a tuneable high repetition rate state-of-the-art NIR laser. This experimental modification will allow us to directly compare live-cell molecular nanomachine activation with both UV and 2PE excitation and exceed the capabilities of a standard off-the-shelf microscope. We have already purchased all associated auxiliary optical components needed for attaching the NIR laser. We advanced the instrument build to a stage, where after sourcing the required laser system a simple 'plug and play' approach will yield the multi-photon upgrade on our instrument within a few weeks. Once fully developed it could form a new extremely high precision biological research tool and opens new horizons toward wound healing and tumour/cancer progression studies. It could pave the way towards a non-invasive treatment of chemotherapeutic agent resistant cancers, such as metastatic breast cancer. This project has a potential game-changing impact on a global scale.