A Titanium-Palladium device to enable the catalytic transformation from a prodrug to an active anticancer drug

Our last paper on the metallurgy of Titanium with a transition metal coating, Palladium, to enable the bioorthogonal chemistry and activate an anticancer prodrug has been published here. It has been the fruits of a collaboration with the BOOM Chemistry Lab at the Edinburgh Cancer Research UK, MRC IGMM, University of Edinburgh.

The survival of people diagnosed with cancer will improve with advances in therapies and the availability of different routes that can be supplementary or even replacements for more aggressive therapies, e.g. chemotherapies that are limited by a lack of selectivity and unwanted side effects. In this paper we propose the initial steps towards a paradigm shift in cancer treatment through the in-situ drug activation and delivery of anti-tumour drugs, applied locally and directly to the cancerous region to minimise those side effects of the more traditional therapies.

To harness the potential of the metal/prodrug interface bio-orthogonal organometallic chemistry, we have developed novel Pd-loaded titanium carriers capable of mediating the spatiotemporal generation of toxic drugs from an inactive precursor (i.e. the prodrug). We have demonstrated this bio-orthogonal activation in lung cell culture conditions, since lung cancer is one of the most prevalent forms of cancer worldwide.

Surface of the Titanium carrier prepared for this application

This experimental study demonstrates how an optimised manufacturing protocol to produce a scaffold can turn it into a therapeutic device through its “switchable” chemistry, and this represents and exciting route towards novel targeted, personalised, tumour-shrinking, cancer treatment therapies.

The paper ‘Design and manufacture of functional catalyst-carrier structures for the bioorthogonal activation of anticancer agents‘ has been published in the New Journal of Chemistry, 2019, 43, 1449 – 1458 DOI: 10.1039/C8NJ05704D

If you would like a free copy of the paper, use this link: here

Manuscript ID: C8NJ05704D, Password: 975964 (get it now! this link will expire on 15th March)

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How pore morphology impacts stiffness

Our most recent study on how pore size, morphology and orientation have an effect on stiffness of a porous alloy has been published in the Journal of Materials Engineering and Performance.

Our article ‘Effect of Pore Size, Morphology and Orientation on the Bulk Stiffness of a Porous Ti35Nb4Sn Alloy‘ describes how the metal foams of a titanium alloy were designed to study porosity as well as pore size and shape independently. These were manufactured using a powder metallurgy/space-holder technique that allowed a fine control of the pore size and morphology; and then characterized and tested against well-established models to predict a relationship between porosity, pore size and shape, and bulk stiffness. Among the typically used correlations, existing power-law models were found to be the best fit for the prediction of macropore morphology against compressive elastic moduli, outperforming other models such as exponential, polynomial or binomial.

The new coefficients reported in this study contribute toward a design tool that allows the tailoring of mechanical properties through porosity macrostructure. The results show that, for the same porosity range, pore shape and orientation have a significant effect on mechanical performance and that they can be predicted. Conversely, pore size has only a mild impact on bulk stiffness.

The full article can be found here

The DOI is https://doi.org/10.1007/s11665-018-3380-0

 

Materials Research Exchange 2018

We spoke at the UK Advanced Material Research & Investor Showcase event in London on 13th March. The event, organised by EPSRC, Innovate UK and KTN, and supported by DSTL, was aimed at materials scientists and engineers who work at the research:industry:academia interface in the UK. It was a fabulous opportunity to learn more about the facilities the UK plcs and Universities have for materials processing and characterization, and also to find out more about the ongoing projects co-sponsored by Innovate UK.

We were invited to present our ongoing project in collaboration with FAR UK Ltd, ‘L3:An Integrated approach towards zero net emissions via lightweight manufacturing’, which is researching how to achieve weight reduction in composites (i.e. fibre-reinforced polymers) without sacrificing mechanical performance, and using a cost effective manufacturing process.

The process under development is one that has the ability to use lower cost composite materials and is inherently near-zero waste, both in its production strategy and also because it does not use environmentally damaging materials.

The process makes porous polymeric structures where the inherent loss of mechanical properties is mitigated by the addition of fibres (initially glass and carbon, expected to be replaced by naturally derived fibres in the near future).  Additionally, the microstructure of the pores and the orientation of the fibres can be controlled in-situ using external means such as sonication and magnetic fields.

This project is allowing us to move forward towards the realisation of topology optimisation and its true implementation for composite manufacturing processes.