The greatest challenge in oncological drug delivery is achieving successful penetration and distribution of the therapeutic agent throughout the tumour: billions of pounds have been spent to date in deploying biochemical approaches in an attempt to solve what is essentially an engineering problem, namely the transport of therapeutics from the blood stream to reach every cancer cell. OxCD3 will seek to transform both clinical and industry practice in drug delivery by demonstrating the value and feasibility of engineering approaches, involving a combination of stimulus-responsive nanocarriers and medical devices already in clinical use, for improved tumour uptake and therapeutic outcome. The Programme Grant will enable the creation of a sustainable, world-unique multi-disciplinary environment for combinational engineering of biology, chemistry and medical devices to improve drug delivery under a single roof. It is also expected to create a unique training environment for the next generation of young scientists working on combination therapies and biomedical nanotechnology, by providing direct exposure to regulatory and manufacturing issues encountered when translating laboratory research into production and clinical practice. A unique feature of the Centre is the capability to design both devices and drug delivery vehicles under a single roof. In the first 5 years, under EPSRC funding, up to 3 carefully selected "Device+Drug" exemplars will be manufactured to GMP, ready for Phase I clinical trials, to provide compelling evidence of feasibility to industrial partners and clinicians; in the next 5 years, a private-public partnership will be built to complete clinical trials of these exemplars using therapeutics of strategic significance to the pharmaceutical industry; beyond 10 years, full industrial sponsorship of the OXCD3 is anticipated, which will focus on addressing next-generation challenges in drug delivery (beyond cancer) in partnership with industry and clinicians. The transformative aim over 50 years is to position the UK as the world leader for multi-disciplinary drug delivery development, complementing its existing position as a drug discovery leader, from design to manufacture and clinical trials.

The 2019 World Health Organisation (WHO) report on Antimicrobial Resistance (AMR) identifies it as: "one of the greatest threats we face as a global community." The evolution of drug-resistant bacteria, our over-use of antibiotics and failure to develop new methods for tackling infection could leave us without viable treatments for even the most trivial infections within the next 3 decades. There have been significant efforts by the WHO and national agencies to raise awareness of AMR and reduce the use of antibiotics, but there is still an urgent need to intensify these efforts and, crucially, to develop alternatives. The aim of the programme is to address this need. The programme will consist of 4 interlinked work packages focussed on the core research objectives: (1) The development of human organoid models for studying interactions between bacteria and the tissue microenvironment and larger scale interactions with the host microbiome. (2) New microscopy methods to complement the organoid models and to facilitate rapid characterisation of bacteria for improved diagnosis. (3) New antimicrobial therapeutics and targeted delivery techniques to improve the use of existing antibiotics and provide viable alternatives. (4) "Drug-free" methods for treating infections and promoting immune function thereby further reducing the use of antibiotics and providing methods suitable for large scale environmental/industrial use. These will be supported by 2 parallel translational activities to enable development of the translational pathway and wider engagement with clinical and industrial stakeholders, policy-makers and the public.

As minimally invasive surgery is being adopted in a wide range of surgical specialties, there is a growing trend in precision surgery, focussing on early malignancies with minimally invasive intervention and greater consideration on patient recovery and quality of life. This requires the development of sophisticated micro-instruments integrated with imaging, sensing, and robotic assistance for micro-surgical tasks. This facilitates management of increasingly small lesions in more remote locations with complex anatomical surroundings. The proposed programme grant seeks to harness different strands of engineering and clinical developments in micro-robotics for precision surgery to establish platform technologies in: 1) micro-fabrication and actuation; 2) micro-manipulation and cooperative robotic control; 3) in vivo microscopic imaging and sensing; 4) intra-operative vision and navigation; and 5) endoluminal platform development. By using endoluminal micro-surgical intervention for gastrointestinal, cardiovascular, lung and breast cancer as the exemplars, we aim to establish a strong technological platform with extensive industrial and wider academic collaboration to support seamless translational research and surgical innovation that are unique internationally.