Biocompatible Polymer Colloids for Bionanotechnology Applications

The three principal scientists in this research programme have highly complementary expertise. Prof. Armes is a synthetic polymer chemist, which means that he designs and makes long-chain molecules. Prof. Ryan is a polymeric materials scientist; his interests lie in the structure and properties of polymers, particularly on the nanometre length scale. Prof. Battaglia is a bio-engineer, who uses his quantitative background to bring academic rigour to the biological sciences. In the last few years, we have worked together (often as pairs, sometimes as a group of three) to conduct numerous inter-disciplinary scientific studies at Sheffield University. This collaborative approach allows us to tackle important scientific problems and questions that we could not contemplate addressing as individual investigators. This Platform Grant will provide us with the opportunity to formalise this ethos and to build a world-class close-knit team over the medium term. Our vision is to conduct transformative research in the area of polymer-based bionanotechnology, which we define as the application of synthetic polymers (man-made long-chain molecules) to solve important biological problems.

This proposal is underpinned by an important breakthrough in the design of bespoke organic nanoparticles recently made by Prof. Armes. His team has developed a robust, patented formulation that enables the efficient synthesis of biocompatible nanoparticles possessing spherical, worm-like or vesicular (i.e. hollow particles) morphologies directly in water using readily available starting materials. We are currently learning the design rules to reliably predict the final particle morphology, which is transforming our understanding compared to the previous ad hoc syntheses described in the literature. This new insight will provide us with an unprecedented opportunity to explore various biomedical applications, including enhanced live cell imaging, thermo-responsive gels for cell culture studies and the efficient delivery of antibodies into cells. Our work will involve the integration of innovative polymer chemistry, state-of-the-art characterisation techniques and world-class bio-engineering to produce a paradigm shift in the fast-moving inter-disciplinary field of bionanotechnology.

We intend to interact fruitfully with an informal network of six named internationally-renowned scientists to access their expertise and instrumentation and hence extract maximum scientific value from this Platform grant. Our post-doctoral scientists will be offered the opportunity to spend up to three months on secondment with our collaborators learning new techniques, experiencing other scientific cultures and enhancing their skill sets. Finally, in addition to our ambitious scientific programme, we intend to provide inspirational leadership and active mentoring for our excellent post-doctoral scientists to enable them to attain their long-term career goals.

All three principal scientists have worked extensively with industrial companies, ranging from the world's largest chemical company (BASF) to a single employee SME. Current sponsors include: P & G, Cytec, Biocompatibles, Reckitt Benckiser, Unilever, AkzoNobel, Croda, Scott Bader, SSL and Vivacta. Thus each Investigator is 'outward-facing' regarding the potential commercial impact of our work and is well aware of the value of IP protection (all are named inventors on multiple patent applications). Thus our team is both well-placed and has the appropriate contacts with various named companies (see case for support) to ensure that any new intellectual property resulting from this project will be fully exploited. Moreover, we have also been active in various outreach activities to communicate our findings to the general public. This is essential to assure the UK tax-payer of the importance of maintaining a long-term strategic investment in scientific research conducted in UK Universities.

All three principal scientists have worked extensively with industrial companies, ranging from the world's largest chemical company (BASF) to a single employee SME. Current sponsors include: P & G, Cytec, Biocompatibles, Reckitt Benckiser, Unilever, AkzoNobel, Croda, Scott Bader, SSL and Vivacta. Thus each Investigator is 'outward-facing' regarding the potential commercial impact of his work and is well aware of the value of IP protection.

Since 1997 Prof. Armes has received continuous funding from Biocompatibles to work on its proprietary monomer, 2-(methacryloyloxy)ethyl phosphorylcholine (MPC). This fruitful strategic collaboration has led to four maintained patents held by Biocompatibles and more than 45 publications with Biocompatibles employees as co-authors. Prof. Battaglia has also enjoyed a close relationship with Biocompatibles since he became an academic in 2006. Indeed, until his recent promotion to a personal Chair, he was the Biocompatibles' Lecturer in Bionanotechnology at U. Sheffield. He has filed four joint patent applications with Biocompatibles, primarily concerning the use of MPC-based copolymer vesicles for the intracellular delivery of bio-active materials (e.g. dyes, DNA etc.). In addition, he has been working with Abcam (a U. Cambridge spin-out with more than 200 employees) to evaluate these vesicles for the intracellular delivery of their commercial antibodies. Hence both Biocompatibles and Abcam are likely to be future beneficiaries of our research programme, once we have utilised the Platform grant to establish a strong independent IP position.

Another potential beneficiary is Polysciences, which has expressed strong interest in adding a Nile Blue vinyl monomer recently prepared in the Armes group to their catalogue range. Prof Armes visited Polysciences in March 2011 and has agreed to send a sample of this compound to this USA-based company in order to test the market. Its emission in the far red region of the visible spectrum is expected to be beneficial for in vitro studies of cells and other biological tissues using either confocal or fluorescence microscopy. We envisage that a second vinyl monomer based on a Cresyl Violet dye may be even more attractive in this regard, particularly as it appears to be a new chemical entity. Once we have optimised the synthesis of this compound, we plan to file a provisional patent application to protect this IP before discussing its commercial potential with third parties. If catalogue sales of such fluorescent labels are successful, this could create a new revenue stream for both Polysciences and the University of Sheffield. If required, toll manufacture of these compounds for Polysciences could be undertaken by Farapack Polymers, a U. Sheffield spin-out company that specialises in monomer/polymer synthesis and related services. This could lead to job creation within the UK.

Since 1995 Prof. Armes has maintained a good relationship with Cognis (Hythe, UK), which manufactures the methacrylic monomers such as glycerol monomethacrylate and 2-hydroxypropyl methacrylate that underpin this Platform grant. Cognis has previously funded a CASE PhD project with Prof. Armes and hosted his visit/lecture in Jan 2009. We will keep this company fully informed of our advances in synthetic polymer chemistry, since this could open up new commercial applications for our copolymers and may also lead to future inward investment by Cognis.

In 2005 U. Sheffield sold its IP rights to Fusion IP in a ten-year pipeline deal. This AIM-listed company has first refusal to commercialise inventions disclosed by University employees. Prof. Armes is currently negotiating with Fusion IP over the formation of a spin-out company to exploit his PCT patent application on RAFT aqueous dispersion polymerisation, which underpins this Platform Grant. Part of the business case for this commercial proposition is based on the potential broad impact of our technology on the life sciences.