Synthesis of glyconanoparticles without protecting groups, published in Bioconjugate Chemistry
Glycans (sugars) dictate a huge range of biological processes, from host-pathogen interactions to cell-cell communication. We have a large research
program into using nanomaterials to display glycans, mimicking how they are presented on cell surfaces. For example, we have used these in diagnostics (including our recent work on rapid COVID diagnostics). However a key challenge is actually getting the glycans on the nanoparticles as multiple protecting groups are often needed. In our latest paper, we installed amino-oxy groups at the end-group of polymers to allow capture of reducing glycans in aqueous solution, with the aim of simplifying our synthetic route with our long-term aim of fully-automating the process. We critically evaluated the efficiency of this reaction using 13-C enriched glucose, to enable the actual polymer, rather than model small molecules to be used. This show 25 % of the chains can capture a glycan, which was then immobilised onto gold nanoparticles. This approach is particularly suited to screening applications where small amounts of glycan are available, to identify hits.
Read the paper here
Cryopreserving Stem Cells with our Polymeric Cryoprotectants Published in ACS Applied Biomaterials
Cryopreservation (freezing) of cells is essential to allow them to be stored and transported. This is especially crucial for emerging stem-cell therapies (i.e. where stem cells are injected into patients, or as part of a biomaterial) where getting the cells from the processing facility to the patient intact, is crucial for a successful therapeutic outcome. In this work, we explored how our new macromolecular cryoprotectants (based on polyampholytes) can be used to reduce the amount of DMSO (dimethyl sulphoxide) required to cryopreserve stems cells, with a focus on retaining their 'function'. We show that we can reduce the DMSO from 10 wt % to 2.5 wt % by adding in our polymers. This decrease in DMSO could be therapeutically useful to reduce side-effects and to simplify processing (due to less DMSO in the mixture post-thaw creating more flexibility in how the cells can be handled). The cells were shown to retain their differentiation ('become other cell types') capability to the same extent as DMSO-alone methods.
This is part of our large research program into innovative cryoprotectants to make cell based therapies and diagnostics cheaper, easier and more readily available.
Read the work here
Viewpoint article on engineering cell surfaces published in ACS Macroletters
Engineering cell surfaces is not trivial. In Nature gene regulation controls protein expression, but we are interested in non-genetic tools to introduce new functionality to cell surfaces, specifically synthetic polymers. In this viewpoint we summarize how the technique of metabolic glycan labeling is being used in polymer/nanoscience to introduce non-natural functionality to cell surfaces. Metabolic glycan labeling allows the introduction of bio-orthogonal handles (e.g. azides) to cells by hijacking glycan biosynthesis pathways by addition of e.g. Azido-N-acetyl mannosamine derivatives, which is processed into sialic acid on the cell surface. This azide (or other functionality) can be used to recruit polymers to the cell surface by formation of a covalent bond. In this article we highlight this really exciting area of biomaterials and summarises some applications including cell-tracking, studying cell-cell communication and more.
This article is part of the 100th Anniversary of Macromolecular Science series.
The Gibson Group is featured on BBC News
On Thursday 25th November, members of our team were interviewed by BBC midlands science correspondent David Gregory. This feature, which was the lead story on BBC Midlands TV news, discussed the teams effort to develop a faster, cheaper and easier to use coronavirus diagnostic. The team are making rapid progress and you can read the story here.
Our latest work on macromolecular cryoprotectants has been published in Biomacromolecules
There is increasing interest in developing new macromolecular cryoprotectants to improve cryopreservation outcomes, however, the criteria used for assessing cryopreservation success varies greatly between studies. In this work we critically analysed the impact of different macromolecular cryoprotectants on post-thaw cell viability and cell recovery, at multiple timepoints, for several cell lines. We found that cell viability was not a good predictor of cryopreservation outcome as it overlooked the number of cells lost during the cryopreservation process. In addition, we showed that it is essential to culture the cells for a period after thawing to allow apoptosis (programmed cell death) to initiate and complete. Considering these findings, we demonstrated that polyampholytes (an emerging class of macromolecular cryoprotectant) are effective cryoprotectants that improve both cell viability and cell recovery, compared to poly(ethylene glycol) which can produce in false positive results.
Read the paper here:
GibsonGroup developing a rapid Coronovirus test
For the past few months the group have been working with Iceni Diagnostics to develop an alternative tool for detecting the novel coronavirus (SARS-COV-2). We have discovered that coronavirus spike proteins (the 'outside of the virus') binds to specific glycans (sugars) and use this to 'capture' it and allow rapid detection using a lateral flow device. Lateral flow devices (e.g home pregnancy test) are easy to use and do not need any training nor infrastructure. We have have proven the principle of this method now, have made prototype devices and are looking to take it (quickly) to the next stage.
Pre-print (NOT PEER REVIEWED) describing the technology is here.
Glyconanomaterials to probe influenza Hemagglutinins is published in Biomacromolecules
Pathogens invade their hosts by several mechanisms including binding to glycans (sugars) on our cell surface. This binding is a crucial stage in their infection cycle and understanding these processes and developing new diagnostics and treatments. In this work we used glycoyslated nanoparticles to investigate how carbohydrate-binding proteins on the surface of influenza (hemagglutinins) bind sialic acids. We used our gold nanoparticle platform to enable easy incorporation of the sialic acids at the ends of polymers immobilised onto the gold particles, ensuring they were colloidally stable but still capable of present the sialic acids. Using a range of assays we optimized their structure to maximise outputs. We then interrogated a panel of hemaglutinins from different influenza strains, including zoonotic (species-crossing) strains. Crucially, when influenza 'jumps species' (e.g. avian to human), the nature of the glycan it binds also changes, which we were able to rapidly map. These results showed that our nanoparticle platform is a suitable tool for interrogating viral surface proteins and for helping to understand zoonosis.
Latest work published in Materials Horizons exploits new polymeric nanomaterials to modulate ice growth.
Polymerisation-induced self-assembly (PISA), a scalable and versatile method to obtain soft nano-objects is utilised for the first time to introduce ice recrystallisation inhibiting (IRI) polymer nanomaterials. Crucially we developed a method to ensure the particles are saline stable which is essential for IRI testing but current PISA formulations cannot tolerate any salt. Uniquely, we achieved this by tuning the core, enabling us to retain our IRI active corona (based on poly(vinyl alcohol)). The resulting particles showed remarkable activity, inhibiting all ice growth below 1 mg.mL-1. These results are significant as they show that Nature’s approach to hyperactivity, based upon aggregation/self-assembly, can be mimicked using polymer self-assembly.