Laser-Guided nanoparticles and Cell Scalextrics
Lead Research Organisation:
Cardiff University
Department Name: Welsh School of Pharmacy
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Publications
Zoriniants G
(2017)
Background-Free 3D Nanometric Localization and Sub-nm Asymmetry Detection of Single Plasmonic Nanoparticles by Four-Wave Mixing Interferometry with Optical Vortices
in Physical Review X
Wymant JM
(2020)
Strategic Trastuzumab Mediated Crosslinking Driving Concomitant HER2 and HER3 Endocytosis and Degradation in Breast Cancer.
in Journal of Cancer
Wymant JM
(2016)
The Role of BCA2 in the Endocytic Trafficking of EGFR and Significance as a Prognostic Biomarker in Cancer.
in Journal of Cancer
Wahlich J
(2019)
Nanomedicines for the Delivery of Biologics.
in Pharmaceutics
Sayers EJ
(2018)
Switching of Macromolecular Ligand Display by Thermoresponsive Polymers Mediates Endocytosis of Multiconjugate Nanoparticles.
in Bioconjugate chemistry
Sayers EJ
(2014)
Distal phenylalanine modification for enhancing cellular delivery of fluorophores, proteins and quantum dots by cell penetrating peptides.
in Journal of controlled release : official journal of the Controlled Release Society
Sayers EJ
(2019)
Endocytic Profiling of Cancer Cell Models Reveals Critical Factors Influencing LNP-Mediated mRNA Delivery and Protein Expression.
in Molecular therapy : the journal of the American Society of Gene Therapy
Sayers EJ
(2014)
Distal phenylalanine modification for enhancing cellular delivery of fluorophores, proteins and quantum dots by cell penetrating peptides.
in Journal of controlled release : official journal of the Controlled Release Society
Sasso L
(2018)
Time and cell-dependent effects of endocytosis inhibitors on the internalization of biomolecule markers and nanomaterials
in Journal of Interdisciplinary Nanomedicine
Pereira P
(2015)
siRNA Inhibition of Endocytic Pathways to Characterize the Cellular Uptake Mechanisms of Folate-Functionalized Glycol Chitosan Nanogels.
in Molecular pharmaceutics
Patel SG
(2019)
Cell-penetrating peptide sequence and modification dependent uptake and subcellular distribution of green florescent protein in different cell lines.
in Scientific reports
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
He L
(2015)
Visualizing Actin Architectures in Cells Incubated with Cell-Penetrating Peptides.
in Methods in molecular biology (Clifton, N.J.)
Giannakopoulou N
(2020)
Four-wave-mixing microscopy reveals non-colocalisation between gold nanoparticles and fluorophore conjugates inside cells.
in Nanoscale
Eissa NG
(2020)
EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide.
in The Biochemical journal
Cleal K
(2013)
Endocytosis, intracellular traffic and fate of cell penetrating peptide based conjugates and nanoparticles.
in Current pharmaceutical design
| Description | Key Findings 1 RECEPTOR CROSSLINKING FOR DRUG DELIVERY Through this award we have discovered a universal strategy for delivering therapeutic entities into cells. It is based on binding receptors on the surface of cells using a targeting entity and then driving a therapeutic into the interior of hte cell to reach its target. The results were published in Molecular Therapy and as recognition of the potential impact of these findings the Journal wrote a two page commentary on this work in the same issue and also included one of our images on the cover. Moody et al Molecular Therapy (2015); 23 12, 1888-1898. doi:10.1038/mt.2015.178 Key KEY FINDINGS 2 MAKING SMART NANOPOLYMERS TO DELIVER THERAPEUTICS Work in collaboration with Nottingham University and the University of Paduva in Italy demonstrated that we could design and synthesis nanoparticles that were in a controlled manner (1 temperature and 2. acidicy) able to bind selectively to cancer cells showing high levels of a target protein on their surfaces. This is work was published via two papers 1) Brazzale et al (2017) Nanoscale DOI: 10.1039/C7NR02595E 2) Sayers et al (2018) Bioconjugate Chemistry DOI: 10.1021/acs.bioconjchem.7b00704 Key Findings 3 POLYMER SCIENCE CAN BE COOL AND EXCITING Through this funding a large science exhibition was organised under the title of "Working Polymers" This was held over a eight day period at the Science and Technology Pavilion of the National Eisteddfod of Wales - Meifod Mid-Wales- August 1 - August 8 2015. The aim of this exhibit was to highlight the science underlying polymers and the fact that we are now totally dependent on them but to also bring introduce EPSRC funded research in the Jones laboratory on the use of polymers for designing nanomedicines to target diseases such as cancer. Approximately 130,000 visited the Eisteddfod over this eight day period and >20,000 were counted into the Science Pavilion. The Exhibit was staffed by Cardiff University academics and undergraduate students. Feedback was extremely positive and there was much discussion surrounding the various polymer activities in display e.g. polymer surface of the world cup rugby ball, nappies and cardiac stents with controlled release of drugs. This also attracted the media and interviews were conducted with BBC Radio and TV and also S4C Wales. A major outcome of these is that the public now clearly view science as a fundamental part of Welsh culture and this is why the Science and Technology Pavilion sits proudly and comfortably at the heart of this very large cultural festival. Key Findings 4 Work initiated during the award have resulted in an important publication in the Journal Nanoscale. This related to using fluorescence to track nanoparticles moving in cells. These particles are of significant interests as vectors for therapeutics and diagnostic agents. Using our newly discovered microscopy technique we have identifies (at the nanoscale) that the fluorescence read out may not perfectly align with the location of the nanoparticle. This has significant implications for the academic and industrial sectors who are studying nanoparticle dynamics in cells. Giannakopoulou et al (202) Nanoscale doi.org/10.1039/C9NR08512B Key Findings 5 During the end of the award the Jones group teamed up with Astra Zeneca who were interested in a paper that was published in 2015 from EPSRC funding (Moody el al Molecular Therapy 2015). This led to a new collaboration and funding and a publication in 2019 where nanoparticles cell interactions have been studied in great detail suing a new technology platform called Endocytic profiling that also involved manufacturing a new reagent for analysing the pH (acidity) in cells. An image from the paper was placed as a cover image Sayers et al 2019: Molecular Therapy https://doi.org/10.1016/j.ymthe.2019.07.018 Cover Image: https://www.sciencedirect.com/journal/molecular-therapy/vol/27/issue/11 |
| Exploitation Route | A. TAKEN FORWARD The results form this paper and thus award have had immediate impact 1 New Grant Funding from Cancer Research Wales . Project Grant October 2015- April 2017 £101,000. 2 New contract and collaboration with Astra Zeneca to develop more efficient drug delivery systems. £135,000 We will continue to apply for funding to study this further with a view to translating the in vitro data into realistic therapeutic strategies. B. USE BY OTHERS 1. We have discovered an approach for receptor targetting, crosslinking and internalization that we believe will be of significant benefit to therapeutic approaches to address a number of diseases with high societal burden such as cancer. We have developed methods for manufacturing new SMART polymer nanoplatforms for delivering therapeutics to cancer cells. In March 10 202 this article has 35 citations 2. We hope that our Endocytic Profile analysis methodological platform and new research tool will be of significant interest to academia and industry. This will allow them to perform more rigorous pre cinical testing in cell models of drug delivery, using nanoparticles and other vectors as delivery platforms |
| Sectors | Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| URL | http://www.nature.com/mt/journal/v23/n12/abs/mt2015178a.html(2)http://pubs.rsc.org/en/content/articlelanding/2017/nr/c7nr02595e#!divAbstract(3)https://pubs.acs.org/doi/10.1021/acs.bioconjchem.7b00704(4)https://www.sciencedirect.com/journal/molecular-therapy/vol/27/issue/11) |
| Description | To provide funding for future Public Engagement activities. To collaborate with industry (Astrazeneca) on delivery of mRNA lipid nanoparticles- 12 month project grant extended to current date in collaborative research towards submission of a manuscript for publication - ongoing Our new Endocytic Platform methodology and pH probe (Sayers et al Molecular Therapy 2019) will be of significant interest to industry. This universal analytcal platform will allow them to perfom more rigourous pre clinical testing of drug delivery performance in cell models for cancer and other diseases. |
| Sector | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Cultural,Societal |
| Description | Cancer Research Wales Project Grant |
| Amount | £101,000 (GBP) |
| Organisation | Cancer Research Wales |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2015 |
| End | 04/2017 |
| Description | Industrial Research Project |
| Amount | £135,000 (GBP) |
| Organisation | AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 04/2016 |
| End | 04/2017 |
| Description | Institutional Strategic Support Fund/Wellcome Trust for Public Engagement |
| Amount | £6,300 (GBP) |
| Organisation | Wellcome Trust |
| Department | Wellcome Trust Institutional Strategic Support Fund |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2016 |
| End | 12/2016 |
| Description | Wellcome Trust Institutional Strategic Support Fund: - Collaboration Panel: Cross-Disciplinary Award |
| Amount | £29,552 (GBP) |
| Organisation | Wellcome Trust |
| Department | Wellcome Trust Institutional Strategic Support Fund |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2017 |
| End | 02/2018 |
| Title | Endocytic Profiling |
| Description | A methodological platform called Endocytic Profiling was developed to characterise the endocytic pathways of pre clinical cell models for drug delivery. A lipid nanoparticle vector enclosing mRNA as cargo was assessed using this platform that identified critical features regulation LNP transfection. We also designed an manufactured a new probe for analysing the pH on the endolysosomal pathway. |
| Type Of Material | Cell line |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | This will be of value to academic and industrial researchers with an interest in preclinical drug delivery analysis of drug delivery vector performance in one of a hundereds of cell models now available. In this respect, the method has significant universality. A manuscript was published on this work in Molecular Therapy that awared the study a cover image. The work was a collaboration between Cardiff University and Astra Zeneca |
| URL | https://www.sciencedirect.com/science/article/abs/pii/S1525001619303570 |
| Title | Receptor Crosslinking |
| Description | The method description is essentially in the title of the manuscript from this EPSRC funded project : Moody et al 2015, Receptor Crosslinking: A General Method to Trigger Internalization and Lysosomal Targeting of Therapeutic Receptor:Ligand Complexes It describes an in vitro crosslinking system that we find is applicable for internalisation of numerous plasma membrane receptors. Crosslinking could be exploited for a wide range of target receptors, for navigating therapeutics through the endolysosomal pathway, for significant therapeutic benefit. |
| Type Of Material | Model of mechanisms or symptoms - in vitro |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | Still very recent but already two new awards have been obatained based on this 2016-2017 Astra Zeneca Research Contract. Cellular Uptake of Drug Delivery Systems Targeting Cancer. A.T. Jones £135,486 2015-2017 Cancer Research Wales Project Grant. Inducing HER2 endocytosis and downregulation via enhanced antibody-receptor clustering as a therapeutic strategy in breast cancer. Jones, A.T., Hiscox, S., Westwell, A. £101,124 |
| URL | http://www.nature.com/mt/journal/v23/n12/full/mt2015178a.html |
| Title | Database for Moody et al 2015 |
| Description | Allt the data supporting the research results reported in EPSRC funded Moody et al (2015); Molercular Therapy 23 12, 1888-1898. doi:10.1038/mt.2015.178 can be accessed via Cardiff University's data catalogue. This includes all the raw data for each indiviual figure via URL http://dx.doi.org/10.17035/d.2015.100121. This URL is displayed on the harcopy and web version of the article. |
| Type Of Material | Database/Collection of data |
| Provided To Others? | No |
| Impact | None yet |
| URL | http://dx.doi.org/10.17035/d.2015.100121. |
| Description | Astra Zeneca Project |
| Organisation | AstraZeneca |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | New collaboration with funding from AstraZeneca starting starting in April 2016 running to June 2017. This stems from EPSRC data presented at Nanotechnologies in Drug Delivery Congress, London, UK 2015 |
| Collaborator Contribution | AZ are synthesise targetted drug delivery vectors in the form of lipid nanaoparticles carrying mRNA for Cardiff University to test in in vitro models Submitted joint Cardiff University - AstraZeneca BBSRC-IPA application. Unsucessful |
| Impact | Presentation of slides at international conferences since 2017. Abstract at International Conference: Puri, S., Ashford, M., Sayers E.J., Jones, A.T. (2018) The Subcellular Profile of Tumour Cells Influences the Intracellular Fate of mRNA Delivery Systems nanoDDS 16th International Nanomedicine & Drug Delivery Symposium, Portland USA. Poster 74 |
| Start Year | 2015 |
| Description | National Eisteddfod of Wales Meifod 2015 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Through EPSRC funding (EP/J021334/1) a large science exhibition was organised under the title of Working Polymers; This was held over a eight day period at the Science and Technology Pavilion of the National Eisteddfod of Wales - Meifod Mid-Wales- August 1 - August 8 and officially opened by the First Minister for Wales Carwyn Jones. The aim of this exhibit was to highlight the science of polymers and the fact that we are now totally dependant on them but to also bring introduce EPSRC funded research in the ATJ laboratory on the use of polymers for designing nanomedicines to target diseases such as cancer. Approximately 130,000 visited the Eisteddfod over this eight day period and >20,000 were counted into the Science Pavilion. The Exhibit was staffed by Cardiff University academics and undergraduate students. Public engagement training was provided for all activity staff by Professor Jones. Feedback was extremely positive and there was much discussion surrounding the various polymer activities in display e.g. surface of rugby balls, nappies, cardiac stents with controlled release of drugs. This also attracted the media and numerous interviews were conducted with BBC Radio and TV and also S4C. A major outcome of these is that the public now clearly view science as a fundamental part of culture and this is why the Science and Technology Pavilion sits proudly and comfortably at the heart of this very large cultural festival. |
| Year(s) Of Engagement Activity | 2015 |
| URL | https://blogs.cardiff.ac.uk/pharmacy-engagement/2015/10/22/national-eisteddfod-2015/ |