Bar-Coded Biomaterials - Designing Self-Authenticating Medicines
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Pharmacy
Abstract
The emerging field of personalised medicine requires a combination of innovative diagnostics, therapeutics and 'point-of-care' use, in order to offer real advantages to industry, clinician and the patient. Materials for detecting and combating disease need be easily assembled, reach their biological targets and release their signals/payloads in precisely controllable and patient-or disease-specific ways. This proposal aims to develop a new class of biomaterial, where the assembly, release and reporting function is explicitly encoded in its structure. These 'Bar-Coded Biomaterials' will have molecular 'ciphers' that can be customised to release signals and drugs according to disease and patient need, and which can also be used to trace and validate the in vivo fate of the drug and carriers. Successful project completion will lead to a new paradigm in functional materials, with impact in future medicine and beyond.
Organisations
- University of Nottingham (Lead Research Organisation)
- University of Nantes (Collaboration)
- University of Liege (Collaboration)
- University of Padova (Collaboration)
- University of Queensland (Collaboration)
- Université Catholique de Louvain (Collaboration)
- University of Angers (Collaboration)
- University of Santiago de Compostela (Collaboration)
- University of Padua (Project Partner)
People |
ORCID iD |
Cameron Alexander (Principal Investigator) |
Publications
Magennis EP
(2017)
Polymers for binding of the gram-positive oral pathogen Streptococcus mutans.
in PloS one
Magennis EP
(2014)
Bacteria-instructed synthesis of polymers for self-selective microbial binding and labelling.
in Nature materials
Magennis EP
(2016)
Engineering serendipity: High-throughput discovery of materials that resist bacterial attachment.
in Acta biomaterialia
Magnusson J
(2011)
Synthetic polymers for biopharmaceutical delivery
in Polym. Chem.
Magnusson JP
(2014)
Programmed assembly of polymer-DNA conjugate nanoparticles with optical readout and sequence-specific activation of biorecognition.
in Nanoscale
Magnusson JP
(2010)
In situ growth of side-chain PEG polymers from functionalized human growth hormone-a new technique for preparation of enhanced protein-polymer conjugates.
in Bioconjugate chemistry
Makwana H
(2017)
Engineered Polymer-Transferrin Conjugates as Self-Assembling Targeted Drug Delivery Systems.
in Biomacromolecules
Mastrotto F
(2013)
pH-responsive poly(4-hydroxybenzoyl methacrylates) - design and engineering of intelligent drug delivery nanovectors
in Polymer Chemistry
Mastrotto F
(2016)
One-pot RAFT and fast polymersomes assembly: a 'beeline' from monomers to drug-loaded nanovectors
in Polymer Chemistry
Mastrotto F
(2013)
Novel pH-responsive nanovectors for controlled release of ionisable drugs.
in Journal of materials chemistry. B
Mitchell D
(2015)
Rational, yet simple, design and synthesis of an antifreeze-protein inspired polymer for cellular cryopreservation
in Chemical Communications
Mitchell DE
(2014)
Quantitative study on the antifreeze protein mimetic ice growth inhibition properties of poly(ampholytes) derived from vinyl-based polymers.
in Biomaterials science
Moloney C
(2023)
Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers.
in Biomaterials science
Monteiro P
(2020)
Synthesis of micellar-like terpolymer nanoparticles with reductively-cleavable cross-links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer
in Journal of Controlled Release
Monteiro PF
(2021)
Reduction-responsive polymers for drug delivery in cancer therapy-Is there anything new to discover?
in Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
Moody PR
(2015)
Receptor Crosslinking: A General Method to Trigger Internalization and Lysosomal Targeting of Therapeutic Receptor:Ligand Complexes.
in Molecular therapy : the journal of the American Society of Gene Therapy
Newland B
(2010)
A highly effective gene delivery vector--hyperbranched poly(2-(dimethylamino)ethyl methacrylate) from in situ deactivation enhanced ATRP.
in Chemical communications (Cambridge, England)
Oelmann S
(2019)
Biocompatible Unimolecular Micelles Obtained via the Passerini Reaction as Versatile Nanocarriers for Potential Medical Applications.
in Biomacromolecules
Pearce AK
(2020)
Effects of Polymer 3D Architecture, Size, and Chemistry on Biological Transport and Drug Delivery In Vitro and in Orthotopic Triple Negative Breast Cancer Models.
in Advanced healthcare materials
Phan H
(2019)
Role of self-assembly conditions and amphiphilic balance on nanoparticle formation of PEG-PDLLA copolymers in aqueous environments
in Journal of Polymer Science Part A: Polymer Chemistry
Powell LG
(2022)
An in vitro investigation of the hepatic toxicity of PEGylated polymeric redox responsive nanoparticles.
in RSC advances
Purdie L
(2016)
Influence of Polymer Size on Uptake and Cytotoxicity of Doxorubicin-Loaded DNA-PEG Conjugates.
in Bioconjugate chemistry
Purdie L
(2018)
Alkyl-Modified Oligonucleotides as Intercalating Vehicles for Doxorubicin Uptake via Albumin Binding.
in Molecular pharmaceutics
Redhead M
(2012)
Relationship between the affinity of PEO-PPO-PEO block copolymers for biological membranes and their cellular effects.
in Pharmaceutical research
Rolfe BE
(2014)
Multimodal polymer nanoparticles with combined 19F magnetic resonance and optical detection for tunable, targeted, multimodal imaging in vivo.
in Journal of the American Chemical Society
Rosengren-Holmberg JP
(2015)
Heparin molecularly imprinted surfaces for the attenuation of complement activation in blood.
in Biomaterials science
Ruiz-Cantu L
(2018)
Synthesis of Methacrylate-Terminated Block Copolymers with Reduced Transesterification by Controlled Ring-Opening Polymerization
in Macromolecular Chemistry and Physics
Saeed A
(2015)
A thermoresponsive and magnetic colloid for 3D cell expansion and reconfiguration.
in Advanced materials (Deerfield Beach, Fla.)
Saeed AO
(2011)
Modular construction of multifunctional bioresponsive cell-targeted nanoparticles for gene delivery.
in Bioconjugate chemistry
Salmaso S
(2009)
Cell up-take control of gold nanoparticles functionalized with a thermoresponsive polymer
in Journal of Materials Chemistry
Sanna M
(2018)
Water Solubility Enhancement of Pyrazolo[3,4-d]pyrimidine Derivatives via Miniaturized Polymer-Drug Microarrays.
in ACS medicinal chemistry letters
Sayers EJ
(2018)
Switching of Macromolecular Ligand Display by Thermoresponsive Polymers Mediates Endocytosis of Multiconjugate Nanoparticles.
in Bioconjugate chemistry
Shahidan NN
(2013)
Hollow colloidosomes prepared using accelerated solvent evaporation.
in Langmuir : the ACS journal of surfaces and colloids
Sicilia G
(2016)
Synthesis of 19 F nucleic acid-polymer conjugates as real-time MRI probes of biorecognition
in Polymer Chemistry
Sicilia G
(2014)
Programmable polymer-DNA hydrogels with dual input and multiscale responses.
in Biomaterials science
Simpson JD
(2021)
Fluorophore Selection and Incorporation Contribute to Permeation and Distribution Behaviors of Hyperbranched Polymers in Multi-Cellular Tumor Spheroids and Xenograft Tumor Models.
in ACS applied bio materials
Soliman M
(2010)
Responsive polyelectrolyte complexes for triggered release of nucleic acid therapeutics.
in Chemical communications (Cambridge, England)
Soliman M
(2011)
Multicomponent Synthetic Polymers with Viral-Mimetic Chemistry for Nucleic Acid Delivery
in Molecular Pharmaceutics
Styliari I
(2018)
High-Throughput Miniaturized Screening of Nanoparticle Formation via Inkjet Printing
in Macromolecular Materials and Engineering
Tai H
(2009)
Thermoresponsive and photocrosslinkable PEGMEMA-PPGMA-EGDMA copolymers from a one-step ATRP synthesis.
in Biomacromolecules
Taresco V
(2020)
Functionalized Block Co-Polymer Pro-Drug Nanoparticles with Anti-Cancer Efficacy in 3D Spheroids and in an Orthotopic Triple Negative Breast Cancer Model
in Advanced Therapeutics
Taresco V
(2016)
Properties of acyl modified poly(glycerol-adipate) comb-like polymers and their self-assembly into nanoparticles.
in Journal of polymer science. Part A, Polymer chemistry
Taresco V
(2016)
New N-acyl amino acid-functionalized biodegradable polyesters for pharmaceutical and biomedical applications
in RSC Advances
Taresco V
(2018)
Stimuli-Responsive Prodrug Chemistries for Drug Delivery
in Advanced Therapeutics
Thurecht KJ
(2010)
Functional hyperbranched polymers: toward targeted in vivo 19F magnetic resonance imaging using designed macromolecules.
in Journal of the American Chemical Society
Travanut A
(2022)
Passerini chemistries for synthesis of polymer pro-drug and polymersome drug delivery nanoparticles.
in Journal of materials chemistry. B
Description | This research project enabled us to develop a family of materials which are encoded with DNA sequences, and which are able to respond to other 'target' DNA sequences to generate a signal or release a drug. The materials typically respond by a change in shape, analogous to a spherical 'box' held together by DNA strands but which can be unlocked by a complementary DNA key. When the 'box' is opened either a drug is released, or some dye molecules move so that the system changes colour. In this way, we have a platform technology which allows us to look for specific DNA sequences or 'keys' and which has an optical or medical readout. In turn this could allow us to personalise the boxes for individual patients |
Exploitation Route | If the price of synthetic DNA or equivalents decreases, there could be use of these materials as sensors and diagnostics, and also as personalised drug delivery systems. The polymers respond to specific DNA or RNA sequences which can be designed in, so allowing the generation of 'bespoke' sensors and therapeutics. In our recent work we have been able to take some of the concepts from this grant to develop materials which are showing promise in anti-cancer applications in pre-clinical studies, and as components of materials for new RNA vaccines. |
Sectors | Chemicals,Digital/Communication/Information Technologies (including Software),Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Security and Diplomacy |
URL | http://www.epsrc.ac.uk/newsevents/news/2014/Pages/molecularnanospies.aspx |
Description | In addition to research, part of this project contributed to the EPSRC Impact Exhibition, and also to YouTube videos which have led to interest in the group and incoming researchers. A number of international conference invitations have arisen, new EU and international networks established and now membership of a large Australian led- transnational Bionanotechnology conmsortium. In addition, an EPSRC-funded Fellowship took on components of this work with AstraZeneca. Although too early for specific non-academic impacts, the new links with AstraZeneca are helping to accelerate an easier path to therapeutic translation.We have had several productive meetings with AstraZeneca, improved our links and numbers of collaborators in AZ. In turn this is helping inform our research so that it is more industry and patient focused. |
First Year Of Impact | 2018 |
Sector | Chemicals,Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Impact Types | Societal,Economic |
Description | Appointment to Chair of EPSRC Physical Sciences Strategic Advisory Team for Physical Sciences |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Description | Appointment to EPSRC Big Ideas Advisory Group |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
URL | https://epsrc.ukri.org/newsevents/news/theworldneedsbigideas/ |
Description | Appointment to the EPSRC Science Engineering and Technology Board |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
URL | https://epsrc.ukri.org/newsevents/news/members-recruited-to-the-epsrc-science-engineering-and-techno... |
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 | Radiotherapy activated materials for enhanced cancer treatments |
Amount | £539,154 (GBP) |
Funding ID | EP/N03371X/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2016 |
End | 11/2018 |
Description | NanoFar |
Organisation | Catholic University of Louvain |
Country | Belgium |
Sector | Academic/University |
PI Contribution | We are the UK host site for NanoFar, the first pan-European Joint Doctorate site in Nanomedicine. We are co-supervising at least 10 PhD projects over the 8 year period of the grant, offering research training linked to our EPSRC Centre for Doctoral Training in Advanced Therapeutics and Nanomedicines. |
Collaborator Contribution | Finance is from the EU via the continental lead, Frank Boury at the University of Angers. Partners provide co-supervision of PhD students, training, access to facilities and instrumentation. |
Impact | This is a multidisciplinary collaboration, linking chemistry, pharmacy, biology and engineering. A number of papers are in preparation from projects, and multiple new personal collaborations are developing. |
Start Year | 2011 |
Description | NanoFar |
Organisation | University of Angers |
Country | France |
Sector | Academic/University |
PI Contribution | We are the UK host site for NanoFar, the first pan-European Joint Doctorate site in Nanomedicine. We are co-supervising at least 10 PhD projects over the 8 year period of the grant, offering research training linked to our EPSRC Centre for Doctoral Training in Advanced Therapeutics and Nanomedicines. |
Collaborator Contribution | Finance is from the EU via the continental lead, Frank Boury at the University of Angers. Partners provide co-supervision of PhD students, training, access to facilities and instrumentation. |
Impact | This is a multidisciplinary collaboration, linking chemistry, pharmacy, biology and engineering. A number of papers are in preparation from projects, and multiple new personal collaborations are developing. |
Start Year | 2011 |
Description | NanoFar |
Organisation | University of Liege |
Country | Belgium |
Sector | Academic/University |
PI Contribution | We are the UK host site for NanoFar, the first pan-European Joint Doctorate site in Nanomedicine. We are co-supervising at least 10 PhD projects over the 8 year period of the grant, offering research training linked to our EPSRC Centre for Doctoral Training in Advanced Therapeutics and Nanomedicines. |
Collaborator Contribution | Finance is from the EU via the continental lead, Frank Boury at the University of Angers. Partners provide co-supervision of PhD students, training, access to facilities and instrumentation. |
Impact | This is a multidisciplinary collaboration, linking chemistry, pharmacy, biology and engineering. A number of papers are in preparation from projects, and multiple new personal collaborations are developing. |
Start Year | 2011 |
Description | NanoFar |
Organisation | University of Nantes |
Country | France |
Sector | Academic/University |
PI Contribution | We are the UK host site for NanoFar, the first pan-European Joint Doctorate site in Nanomedicine. We are co-supervising at least 10 PhD projects over the 8 year period of the grant, offering research training linked to our EPSRC Centre for Doctoral Training in Advanced Therapeutics and Nanomedicines. |
Collaborator Contribution | Finance is from the EU via the continental lead, Frank Boury at the University of Angers. Partners provide co-supervision of PhD students, training, access to facilities and instrumentation. |
Impact | This is a multidisciplinary collaboration, linking chemistry, pharmacy, biology and engineering. A number of papers are in preparation from projects, and multiple new personal collaborations are developing. |
Start Year | 2011 |
Description | NanoFar |
Organisation | University of Santiago de Compostela |
Country | Spain |
Sector | Academic/University |
PI Contribution | We are the UK host site for NanoFar, the first pan-European Joint Doctorate site in Nanomedicine. We are co-supervising at least 10 PhD projects over the 8 year period of the grant, offering research training linked to our EPSRC Centre for Doctoral Training in Advanced Therapeutics and Nanomedicines. |
Collaborator Contribution | Finance is from the EU via the continental lead, Frank Boury at the University of Angers. Partners provide co-supervision of PhD students, training, access to facilities and instrumentation. |
Impact | This is a multidisciplinary collaboration, linking chemistry, pharmacy, biology and engineering. A number of papers are in preparation from projects, and multiple new personal collaborations are developing. |
Start Year | 2011 |
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 | University of Queensland |
Organisation | University of Queensland |
Country | Australia |
Sector | Academic/University |
PI Contribution | We have shared data, materials, hosted and sent research students and post-docs for our collaborations |
Collaborator Contribution | Our partners have provided, expertise, materials and access to high end medical imaging facilities. |
Impact | Multiple papers > 10 date Grants: DP140100951. ARC Discovery Projects. Multifunctional and Multimodal Theranostics: Manipulating Material Properties for Advanced Diagnostics. Total funding 450,264 $AUS. C Alexander (Nottingham, UK Co-I) CE140100036: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology. Led from Monash (Prof T Davis). Total funding 27,996,624 $AUS. C Alexander (Nottingham), UK Co-I and member of proposal lead team. 2014-2021. |
Start Year | 2008 |
Description | EPSRC IMPACT! Exhibition |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Exhibition or artwork designed by James King based on projects in the "Chell" project and my Leadership Fellowship grant. Artwork and film to explore concepts in what products from synthetic biology might look like Requests for articles and participation in further Synthetic Biology dialogues |
Year(s) Of Engagement Activity | 2010 |
Description | Invited talk (Queensland) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited to give a talk on "Responsive Polymers as Site-Activated Nanomediences" at AIBM, University of Queensland on 7th April 2011. Audience of academics and postgraduate students. |
Year(s) Of Engagement Activity | 2011 |
Description | Invited talk (Sydney) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Talk given to academics and postgraduate students at the University of Sydney on 'New developments in "Stimuli-Responsive Biomedical Polymers"' on 8th April 2011. |
Year(s) Of Engagement Activity | 2011 |
Description | Publication and feature in EPSRC Pioneer Magazine |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Feature article in Pioneer 9 regarding Leadership Fellowship and also leading the EPSRC/AstraZeneca/Nottingham Centre for Doctoral Training in Targeted Therapeutics. http://www.epsrc.ac.uk/newsevents/pubs/mags/pioneer/Pages/pioneerdownloads.aspx . Queries from journalists and subsequent press releases |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.epsrc.ac.uk/newsevents/pubs/mags/pioneer/Pages/pioneerdownloads.aspx |
Description | Royal Society Summer Exhibition |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Exhibition as part of EPSRC grants in 3D Biomaterials, Bioresorbable materials and Fellowships, to show non-specialists the role of polymers in everyday medicines, and in medicines/medical devices of the future. |
Year(s) Of Engagement Activity | 2016 |
URL | https://royalsociety.org/science-events-and-lectures/summer-science-exhibition/exhibits/plastic-insi... |
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 |
Description | YouTube 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 | Podcast developed by journalist Brady Haran to disseminate information regarding science at Nottingham. Ongoing videos as part of Brady Haran's 'Test-Tube' science video series I received numerous requests to participate in new research programs, and enquiries from potential PhD students. |
Year(s) Of Engagement Activity | 2008,2010,2012 |
URL | http://www.tes.co.uk/teaching-resource/Cameron-Alexander-Interview-6394346 |