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.
People |
ORCID iD |
| Cameron Alexander (Principal Investigator) |
Publications
Mastrotto F
(2013)
pH-responsive poly(4-hydroxybenzoyl methacrylates) - design and engineering of intelligent drug delivery nanovectors
in Polymer Chemistry
Alexander, C.
(2011)
Comprehensive Biomaterials
| 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, started work 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 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. Dr Matini was rapidly promoted, and is now a Project Officer and Impact Acceleration Coordinator for the Green Chemicals Beacon of Excellence at Nottingham, helping a range of companies link to research in materials at Nottingham. |
| Sector | Agriculture, Food and Drink,Chemicals,Education,Energy,Healthcare,Manufacturing, including Industrial Biotechology,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 | Public |
| 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 | Academic/University |
| 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 |