A novel radiolabelled multimodal nanocarrier system for tracking the delivery of therapeutic drugs and radionuclides in hard-to-treat cancers

Cancer is the second leading cause of death worldwide, with only 50% of diagnosed patients surviving a more than 10 years. Therapy using traditional chemotherapeutics is hindered due to lack of specificity, poor solubility and distribution of the drugs, unfavourable pharmacokinetics, and toxicity to healthy cells which results in severe side effects. The field of cancer theranostics has generated a vast amount of excitement due to the innovative ability to increase therapeutic selection on the basis of specific molecular disease hallmarks, improved foresight of possible adverse effects, and novel methods to empirically monitor response to the therapy. Targeted drug delivery systems are explored for the design of smart therapies capable of selective delivery of toxic drugs while also enabling detection of the delivery and post-drug release fate. In this project, we aim to reduce off-target toxicities and increase concentrations of therapeutic drugs in target organs. Combining effective cancer treatment with targeting abilities, paired with imaging and therapeutic efficiency will be a unique addition to the field of cancer nanomedicine. By achieving these objectives, this research will contribute a successful proof-of-concept therapy, which will greatly reduce off-target toxicities and increase overall therapy success.

This interdisciplinary project will harness knowledge across numerous departments at the University of Cambridge, and further expertise from Hitachi. The project will involve the synthesis of a multimodal nanocarrier system using porous polydopamine (PDA) nanocarriers decorated with chelating agents for binding radionuclides for imaging, capable of embedding the drug molecules within their cores and containing functional groups to bind cancer cell specific targeting agents for hard-to-treat cancers. Targeting agents will be explored in collaboration with Dr Daniel Munoz-Espin's group. The nanocarrier system will be assessed at each stage using both gold standard and novel state-of-the art technologies. Small animal PET studies will be carried out to gain important information on biodistribution.

The main outcome from this project will be the advancement of novel treatments for hard-to-treat cancers. In the long term, the research will contribute to the improvement of patient outcomes and quality of life by increasing the concentration and specificity of drugs that reach the tumour site. In the short term, clinicians, patients, regulatory authorities, and other stakeholders will benefit from the early involvement for a novel therapeutic solution. Researchers will benefit from the new scientific approaches and engineering methods that will be explored in this interdisciplinary project. The project optimises diagnosis and treatment and aids in the creation of novel therapies and approaches to drug delivery and targeted medicine. This project is aligned with the EPSRC's clinical technologies research area, with the help of the dynamic fields of bionanotechnology, drug delivery, radiology, and medical imaging.

The primary outputs from the CDT will be cohorts of highly qualified, interdisciplinary postgraduates who are experts in a wide range of sensing activities. They will benefit from a world leading training experience that recognises sensor research as an academic discipline in its own right. The students will be taught in all aspects of Sensor Technologies, ranging from the physical and chemical principles of sensing, to sensor design, data capture and processing, all the way to applications and opportunities for commercialisation, with a strong focus in entrepreneurship, technology translation and responsible leadership. Students will learn in extensive team and cohort engaging activities, and have access to cutting-edge expertise and infrastructure. 90 academics from 15 different departments participate in the programme and more than 40 industrial partners are actively involved in delivering research and business leadership training, offering perspectives for impact and translation and opportunities for internships and secondments. End users associated with the CDT will benefit from the availability of outstanding, highly qualified and motivated PhD students, access to shared infrastructure, and a huge range of academic and industrial contacts.

Immediate beneficiaries of our CDT will be our core industrial consortium partners (MedImmune, Alphasense, Fluidic Analytics, ioLight, NokiaBell, Cambridge Display Technologies, Teraview, Zimmer and Peacock, Panaxium, Silicon Microgravity, etc., see various LoS) who incorporate our cross-leverage funding model into their corporate research strategies. Small companies and start-ups particularly benefit from the flexibility of the partnerships we can offer. We will engage through weekly industry seminars and monthly Sensor Cafés, where SME employees can interact directly with the CDT students and PIs, provide training in topical areas, and, in turn, gain themselves access to CDT infrastructure and training. Ideas can be rapidly tested through industrially focused miniprojects and promising leads developed into funded PhD programmes, for which leveraged funding is available through the CDT.

Government departments and large research initiatives are formally connected to the CDT, including the Department for the Environment, Food and Rural Affairs (DEFRA); the Cambridge Centre for Smart Infrastructure and Construction (CSIC); the Centre for Global Equality (CGE); the National Physics Laboratory (NPL); the British Antarctic Survey (BAS), who all push our CDT to generate impacts that are in the public interest and relevant for a healthy and sustainable future society. With their input, we will tackle projects on assisted living technologies for the ageing population, diagnostics of environmental toxins in the developing world, and sensor technologies that help replace the use of animals in research. Developing countries will benefit through our emphasis on open technologies / open innovation and our exploration of responsible, ethical, and transparent business models. In the UK, our CDT will engage directly with the public sector and national policy makers and regulators (DEFRA, and the National Health Service - NHS) and, with their input, students are trained on impact and technology translation, ethics, and regulatory frameworks.