EPSRC IRC in Targeted Delivery for Hard-to-Treat Cancers

Lead Research Organisation: University of Cambridge
Department Name: Engineering

Abstract

While the survival rate for most cancers has doubled over the last 40 years, hard-to-treat cancers show survival rates below 14%. To combat these cancers, multiple pathways (immune/inflammatory, neoangiogenic, cell replication) need to be targeted and this necessitates a multimodal delivery approach that will increase not only the amount but also the range of therapeutic agents that reach the target site. This IRC will address this challenge by developing (i) delivery vehicles that are based on metal organic frameworks and organic cages and show substantially increased payload capacity, and (ii) implantable/injectable delivery platforms that are based on gels and electrophoretic pumps and enhance drug penetration through e.g. the blood-brain barrier. By combining these two approaches, we will achieve a step change in the amount and range of drugs that reach the tumour site. Two crosscutting translational activities, on material delivery & additive manufacturing and on validation, will consider the whole chain from the conception of the delivery system to its clinical application, leading to a holistic approach to the problem of targeted drug delivery. The proposed research program builds on an institutional-level initiative on therapeutic science and strong links with CRUK and with national labs and industry leaders in drug development. The interdisciplinary team involved in this IRC includes groups from five universities with expertise ranging from materials synthesis and characterisation, through device engineering and manufacturing, to pharmacology and cancer, and will deliver scientific breakthroughs that extend beyond the field of targeted drug delivery. Economic and societal impacts will be delivered and measured through a joined-up approach to market analysis, industry feedback and embedded anticipation of risks to translation. Engagement of end-users and stakeholders, which will begin as early as the preparation of the second-round proposal, will play a critical role in steering the IRC throughout its lifetime.

Planned Impact

The chief impact from this project will be the development of new treatments for hard-to-treat cancers. Over the long term, these treatments will improve patient outcomes and quality of life by increasing the amount and range of drugs that reach the tumour site. In the short term, stakeholders and end-users including clinicians, patient groups, regulatory agencies and members of the healthcare technology supply chain, will benefit from the creation of an ecosystem that engages them at the early stages of the generation of a novel therapeutic solution. Industry will benefit by participating in a project that brings together state-of-the-art materials and device solutions to the field of drug delivery in a way that de-risks their transition to the market. The general public will benefit from a wide range of outreach events that target increased awareness of the future of medical treatments. The academic community will benefit from new scientific knowledge and engineering solutions that will be created by this interdisciplinary project.

Publications

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Germain M (2020) Delivering the power of nanomedicine to patients today. in Journal of controlled release : official journal of the Controlled Release Society

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Kubánková M (2018) Rotor-Based Organelle Viscosity Imaging in Biophysical Journal

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Kubánková M (2019) Linker length affects photostability of protein-targeted sensor of cellular microviscosity. in Methods and applications in fluorescence

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Marciniak S (2019) Endoplasmic reticulum stress: a key player in human disease in The FEBS Journal

 
Description EPSRC Impact Acceleration Account
Amount £8,078 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2019 
End 12/2019
 
Description WELLCOME TRUST - INSTITUTIONAL TRANSLATION PARTNERSHIP AWARD: UNIVERSITY OF CAMBRIDGE
Amount £50,000 (GBP)
Funding ID RG93172 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 05/2020
 
Description IRC-ARM 
Organisation ARM Holdings
Country United Kingdom 
Sector Private 
PI Contribution Hosting a meeting to discuss collaborative opportunities
Collaborator Contribution None as yet
Impact None as yet
Start Year 2018
 
Description IRC-AZ 
Organisation AstraZeneca
Department Research and Development AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Expertise in the devices and chemistries being deployed as part of the project.
Collaborator Contribution AstraZeneca have provided expertise in drug delivery by providing a representative to sit on the steering committee for the project. They have also contributed by providing guidance in developing target product profiles and hosting a meeting to explore wider possibilities for collaboration. In addition to in-kind support AstraZeneca have also provided substantial additional funding for translation work on hydrogels for the treatment of glioblastoma
Impact This is a multidisciplinary collaboration involving engineers, chemists and clinicians. The main outcome of the collaboration to-date has been to assist in shaping the strategic direction of the IRC.
Start Year 2019
 
Description IRC-CPI 
Organisation Centre for Process Innovation (CPI)
Country United Kingdom 
Sector Private 
PI Contribution Expertise in the technologies we are developing
Collaborator Contribution Expertise in high value manufacturing
Impact Assistance in shaping the approach we have taken to the manufacturing challenges associated with the project
Start Year 2019
 
Description IRC-MDC 
Organisation Medicines Discovery Catapult
Country United Kingdom 
Sector Private 
PI Contribution Expertise in the drug delivery technologies being developed
Collaborator Contribution Assistance in identifying possible additional project partners
Impact Contacts made with potential industrial collaborators
Start Year 2018
 
Description IRC-NPL 
Organisation National Physical Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in the drug delivery technologies being developed.
Collaborator Contribution Expertise in medical instrumentation and mass spectrometry imaging
Impact No outcomes as yet
Start Year 2018
 
Description BBC1 Naked scientist Question time guest 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Ljiljana Fruk joined a group of Panelist to answer the questions from the listeners concerning chemistry, nanotechnology and nano medicine in BB1 Naked scientist question time
Year(s) Of Engagement Activity 2019
URL https://www.thenakedscientists.com/podcasts/naked-scientists-podcast/extremely-curious-qna
 
Description Cambridge Experimental Cancer Medicine Centre PPI Panel 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Presentation to Cambridge Experimental Cancer Medicine Centre Patient and Public Involvement Panel to inform them of our progress and to obtain their input on which drugs to use (tried and tested versus novel molecularly targeted therapies) and on design of implantable devices.
Year(s) Of Engagement Activity 2019
 
Description Cambridge Philosophical Society invited lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Cambridge Philosophical Society talks are aimed at general public and the member of the University of Cambridge, and the lecturers are invited based on their expertise and ability to engage audiences with their chosen topic. The topic was Modern Molecular Science and how is it changing our life.
Year(s) Of Engagement Activity 2020
URL https://www.cambridgephilosophicalsociety.org/lectures-visits/modern-molecular-science-and-how-it-ch...
 
Description Cambridge Science Festival March 2019 hands-on microscopy activities for the general public (all ages) over two weekends. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact The Cambridge Science Festival is a series of events held annually in March in Cambridge, and is the United Kingdom's largest free science festival.[1] The festival attracts more than 30,000 visitors to over 250 events.[2] University researches and students open their lecture halls and laboratories to the general public, and hold Talks, Exhibitions and Demonstrations, mostly free of charge.[1]

The Marciniak lab plays a leading part in representing the Cambridge Institute for Medical Research (CIMR) in organising hands on cell biology activities. For young children these involve toys and games teaching about the structure of cells. For older children and adults, we use a variety of microscopes including fluorescence microscopy to illustrate how modern microscopy aids in the understanding of the molecular cell biology of disease.


[1] "University of Cambridge Science Festival 2011". BBC News. Retrieved 21 March 2015.
[2] "About - www.sciencefestival.cam.ac.uk". Retrieved 21 March 2015.
Year(s) Of Engagement Activity 2015,2016,2017,2018,2019
URL https://www.sciencefestival.cam.ac.uk/events/grander-view-how-modern-microscopy-illuminates-disease
 
Description Conference presentation by Dr Niamh Willis-Fox at The Inkjet Conference 2019, Dusseldorf. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Conference presentation by Dr Niamh Willis-Fox at The Inkjet Conference 2019, Dusseldorf. This is the major industry-academic joint conference that looks at inkjet technologies.
Year(s) Of Engagement Activity 2019
 
Description Creation and distribution of the publication - The IfM colouring book "How Stuff Gets Made". 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Creation and distribution of the publication - The IfM colouring book "How Stuff Gets Made". This outreach activity was a highly popular contribution to the Cambridge Science Festival 2019 by the postdoctoral researcher on this grant Dr. Niamh Willis-Fox.
Year(s) Of Engagement Activity 2019
 
Description IRC website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Website giving details of the work undertaken by the IRC, and contact details
Year(s) Of Engagement Activity 2019
 
Description Keynote talk at Nanotexnology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Keynote talk at nanotechnology conference, attended by physical scientist and engineers
Year(s) Of Engagement Activity 2019
URL https://www.nanotexnology.com/2019/
 
Description Pint of Science talk by Ljiljana Fruk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact A presentation by Ljiljana Fruk (Co-PI on the award) as part of the Pint of Science series of talks. As well as the talk by an IRC Co- PI the event was sponsored by the IRC, publicising its activities to an audience who may not attend more formal presentations
Year(s) Of Engagement Activity 2019
 
Description Plenary talk at EANS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary talk at the European Association of Neurosurgical Societies, attended mostly by clinicians
Year(s) Of Engagement Activity 2019
URL https://eans2019.com/
 
Description Plenary talk at Fpi14 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary talk at the 14th International Symposium on Functional p-Electron Systems (Fp14) in Berlin
Year(s) Of Engagement Activity 2019
URL http://www.fpi14.de
 
Description Plenary talk at International Conference for Flexible Electronics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary talk at probably largest Flexible Electronics meeting in Asia
Year(s) Of Engagement Activity 2019
URL http://icfe.gfeit.com/
 
Description Plenary talk at MNE 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary talk at key microfabrication conference attended by scientists and engineers
Year(s) Of Engagement Activity 2019
URL https://www.mne2019.org/
 
Description Plenary talk at ORBITALY 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary talk at ORBITALY, attended by scientists interested in applications of organic electronic materials in biology
Year(s) Of Engagement Activity 2019
URL https://www.orbitaly2019.eu/
 
Description Project Partners Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A meeting to engage with potential partners with expertise in drug delivery technologies.These included small biotech companies, contract research organisations, pharma and engineering companies as well as charity representatives
Year(s) Of Engagement Activity 2019
 
Description Seminar - Constantin C. Coussios 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Seminar by Professor Constantin C. Coussios addressing attendees from various departments, including discussions on future collaborations
Year(s) Of Engagement Activity 2019
 
Description Seminar - Uli Weisner 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Seminar by Professor Uli Weisner (Cornell University) to research community at University of Cambridge
Year(s) Of Engagement Activity 2019
 
Description Seminar -Snow Stolnik & Cameron Alexander 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact A seminar attended by academics/researchers from various departments within University of Cambridge, followed by disucssions of how to collaborate more closely in future,
Year(s) Of Engagement Activity 2019
 
Description TEDx talk Dusseldorf 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Talk by Ljiljana Fruk at TEDxKoenigsallee in Düsseldorf within the theme "Outside the Bubble"
Year(s) Of Engagement Activity 2019
 
Description Talk at EuroMOF 2019, Paris. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact European MOF conference
Year(s) Of Engagement Activity 2019
 
Description Talk at public outreach event organised by Fundación Ramón Areces 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk on symposium organised by Fundación Ramón Areces, attended by the general public
Year(s) Of Engagement Activity 2020
URL https://www.fundacionareces.es/fundacionareces/en/events/biomimetic-sensors-their-use-and-potential-...
 
Description Twitter account 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Twitter account established to dissemenate news relevant to the work of the IRC
Year(s) Of Engagement Activity 2019