Self-Assembling Therapeutics for Specific Nanoscale Interactions with the Sodium Pump

Lead Research Organisation: University of Nottingham
Department Name: Sch of Pharmacy

Abstract

The long-term science for this project is directed towards the preparation of new and effective therapeutics, and to dothis we need to ensure that our novel devices hit their biological targets and have proven efficacyin a particular disease application before we can commence a larger programme to guide theirdevelopment towards clinical practice. The European Science Foundation (ESF) Nanomedicine Forward Look describes the development ofnew multifunctional, spatially ordered, architecturally-varied systems for targeted drug delivery as apriority. Nanopharmaceuticals based on antibody-drug conjugates and polymer-biopolymerconjugates are a key component of enhanced efficacy medicines. While more complex, theseconjugates offer enhanced diversity, leading to drugs with much higher information content comparedto small molecule compounds. This allows for greater target specificity, improved functionality andthe opportunity to multi-task, for example to diagnose and treat in situ, or to act on more than onetherapeutic target or disease pathway simultaneously. The novel conjugate nanodevices we willprepare in this programme are thus uniquely able to address diseases which are inadequately treatednow. By exploiting new biological targets and interfaces, our materials will contribute a vital step inimproving patient, economic and society outcomes arising from disease.

Publications

10 25 50
 
Description This project developed new polymer materials which form virus-sized compartments, and which can be used to encapsulate genetic fragments which may find use in gene therapy. The polymers change their shape in response to the changes of pH found in some cancerous tissues, and so transform from a capsule-type material to single free chains. In the container form, it was possible to include nucleic acids as prototype fragments for gene therapy, whereas in the single chain form, nucleic acid encapsulation was not possible, thus we were able to trigger release of the nucleic acids in cancer cells.
We also used variants of these materials on gold particles, and showed that a temperature increase to 40C (as occurs in some solid tumours) was able to change the display of targeting groups on the particles. This allowed us to deliver the gold particles specifically to cancer cells by a disease-relevant temperature change.
Exploitation Route We have taken some of the findings, and are developing these in collaboration with Cardiff University and the University of Padova in EPSRC Grant EP/J021180/1.
Other groups are developing materials similar to ours for cancer therapy, and we are in discussions with several lopment.companies for further dev
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://pubs.rsc.org/en/content/articlelanding/2013/py/c3py00744h#!divAbstract
 
Description Findings from this work have informed the translational path for therapeutics. A researcher from the project, Dr Teresa Matini, now works as Research Project Manager at Nottingham Trent University, with a specific goal of enhancing impact and translation of biomedical research. She has helped prepare funding bids, drawing on her knowledge gained from the project, which are helping to bring in investment from industry. Dr Matini has now returned to Nottingham University as an Impact Project Officer, collating Impact Case Studies and working with researcher teams to enhance the exploitation of their research beyond the academy
Sector Education,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Programme Grant
Amount £5,365,958 (GBP)
Funding ID EP/N006615/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 11/2015 
End 11/2020
 
Description CIPF Valencia 
Organisation Regional Government of Valencia
Department Príncipe Felipe Research Centre (CIPF)
Country Spain 
Sector Charity/Non Profit 
PI Contribution We have provided materials, training in polymer synthesis and access to instrumentation for researchers from CIPF during research stays.
Collaborator Contribution Secondments of PhD students and PDRAS to our labs and hosting of our PhD students for access to advanced cell culture techniques and facilities
Impact Papers (1 published, 1 in press and several in draft) EU grant Multidisciplinary training (pharmacy, chemistry, cell biology) Recruitment to UK- Dr Joachin Sanchis, PDRA on the grant EP/H006915/1 is now a Lecturer in the Warwick /Monash partnership.
Start Year 2009
 
Description University of Padova 
Organisation University of Padova
Country Italy 
Sector Academic/University 
PI Contribution We have hosted a number of Masters and PhD students for research stays. We have provided materials, training in polymer synthesis, access to instrumentation and facilities.
Collaborator Contribution Excellent Masters students, of which 6 have stayed on to carry out PhD studies in Nottingham. The Padova group have also hosted our PhD students and PDRAs, giving hem training in pharmaceutical formulation science and pharmacokinetics.
Impact Multiple papers (> 10) EU/EPSRC Grants (Value > 500,000 GBP) Multidisciplinary (pharmacy, pharmacology, chemistry)
Start Year 2006
 
Description Web videos 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Web-based videos produced and devised by journalist Brady Haran featuring science at Nottingham.

Series of videos describing science and scientists at Nottingham

Journalists asked for interviews
Year(s) Of Engagement Activity 2009
URL http://www.youtube.com/watch?v=ThgJHeDKsxA