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Paper Published in Macroletters

Our latest work has been published in ACS Macro Letters. In this work we describe a new mehtod to covalent attached synthetic polymers to cell surfaces, enabling us to bring new functionality to them, without resorting to genetic methods. There already exist many chemistry for targetting cell surfaces, such as simple NHS esters, or lipid insertion, but we wanted to form a directed, covalent bond. Glycan metabolic labelling was exploited, whereby we added an azido-functional ManNac (a sugar) to the cells, which can be processed such that it presented an azide on the cell surface as a sialic acid. We then made telechelic polymers used RAFT, adding an azide reactive strained alkyne at one end, and a fluorophore or biotin at the other. We would able to show selective conjugation and coating of the cells using these polymers, with no evidence of cytoxocity nor of morphological changes (i.e. the cells looked happy). To show that we can use this method to change the functionality of the cells, we were able to recruit strepavidin to the cell surfaces, targetting the biotin units on the polymer, which did not occur without the polymer. We think this method could be broadly used to add synthetic polymers to cell surfaces to modify their function, which may have application in therapies, cell tracking and also to ask fundamental questions about how this modification affects cell function.

Read the paper here

Engineering Cell Surfaces by Covalent Grafting of Synthetic Polymers to Metabolically-Labeled Glycans

Thu 11 Oct 2018, 11:01 | Tags: Group News, Publication

Paper Published in Langmuir

Our latest work has been published in Langmuir, as part of a special issue focussed on Mechano- and Cryo-biology, which we were very proud to be invited to contributed too. In this work, we ask the question of 'do our antifreeze-protein mimetic polymers function the same in nanoparticle form, as in solution'. This might seem straightforward, as we know that increasing the molecular weight of our polymers, increases their activity, hence when immobilised on a nanoparticle they might be more active. We actually saw that there was no enhancement, but also no decrease (which again is a surprise as the nanoparticles have a lower molar concentration than free polymers). We made use of RAFT/MADIX polymerization to make thiol-terminated poly(vinyl alcohol) to coat gold nanopartices for this particular work, as model nanoparticle systems, which were tunable in terms of size and composition.

Read the paper here;

Multivalent Presentation of Ice Recrystallization Inhibiting Polymers on Nanoparticles Retains Activity

Thu 11 Oct 2018, 09:23 | Tags: Group News, Publication

Paper in ChemEurJ; Hot paper and Media Attention

Our latest work into developing non-traditional antimicrobial agents has been published in Chemistry: A European Journal. This continues our research into cationic polymers as antimicrobial agents. In this new work, we demonstrate a semi-automated synthesis platform, which can use robotics to speed up the liquid handling, alongside exploiting photo-chemical polymerization to enable this to take place in 'open air'; this is a key step as it removes the need for sealed vials and allowed us to polymerise directly in 96 well plates. 96 well plates are industry-standard for biological screening, which enabled us to rapidly screen ~ 100 polymers for antimicrobial activity, as well as blood compatability. Using this high-throughoput approach a surprising 'hit' was found, where including 15 mol % of oligopropyleneglycol methacrylate lead to a dramatic enhancement in bacteriostatic activity, but without introducing bacteriocidal activity.

Read the paper here

Photochemical 'In-Air' Combinatorial Discovery of Antimicrobial Copolymers

The paper was also featured in the media, and highlighted by the reviewers as being a 'hot' paper.

Wed 29 Aug 2018, 12:39 | Tags: Group News, Publication

Paper Published in Biomacromolecules

Our latest cryopreservation work has been published in Biomacromolecules. This work describes the development of an 'all-polymer' cryopreservation formulation for bacteria. Bacteria are used routinely in all molecular and structural biology labs around the world, and are key in many biotechnology and food processes (e.g. 'friendly bacteria' in yoghurts). The bacteria are not kept continously growing, but are stored as stocks, using glycerol to reduce ice-induced damage in freezers. In this work, we were inspired by antifreeze proteins which let extreomphile species survive in the coldest places on earth, but used synthetic polymers, which are cheaper, more scalable and practical for daily use. We have previously shown that polymer mimics of antifreeze proteins can protect mammalian cells in DMSO-mediated cryopreservation, but the mechanisms of stress (and recovery) from cold are very different in bacteria. Here we simply used precise ratios of PEG and PVA (both are food-safe, low cost commodity polymers) and show we can match, or outperform, glycerol in several bacteria storage scenarios.

Read the paper here;

Ice Recrystallization Inhibiting Polymers Enable Glycerol-Free Cryopreservation of Microorganisms

Mon 06 Aug 2018, 10:38 | Tags: Group News, Publication

Paper Published in ACS Central Science

Our latest work, from Lewis' PhD in collaboration with the O'Reilly Group (formally Warwick, now Birmingham) has been published in ACS Central Science. This work proposes a new method to retain the function of therapeutic (or other) enzymes without needing covalent conjugation. Traditional strategies to improve the pharmacokinetics of protein drugs involve addition of polymers (such as PEG) to the protein to reduce proteolytic degredation and immune responses. In this work we packaged enzymes inside a polymeric vesicle by in situ PISA (polymerization induced self assembly). We showed that the PISA process enables full retention of protein activity. However, most improtanlty we observed that the poly(hydroxylpropylmethacrylate) component was selctively permeable to small molecules - this meant the enzynme could peform its catalytic function, but larger molecules, such as proteins, could not access it. Using this strategy asparaginase was encapsulated in the vesicle and shown using a cell-based assay that it retained it is therapeutic function. We feel this offers a new opportunity in molecular sieving and will have broad application

Read the paper here

Confinement of therapeutic enzymes in selectively permeable polymer vesicles by polymerization-induced self-assembly (PISA) reduces antibody binding and proteolytic susceptibility'

Thu 17 May 2018, 14:28 | Tags: Publication

Paper published in JACS!

Our latest work on trying to understand, and mimic, how antifreeze glycoproteins (AFGPs) function to slow ice growth has been published in the Journal of the American Chemical Society. AFGPs have several macroscopic properties due to their ability to influence ice crystal growth but it is not fully clear how they work, or how they recognise ice faces. There is no crystal structure of antifreeze proteins, so the 3-D structural information is still missing. In this work, we build upon our previous observations that amphipathic helicies (compounds with hydrophilic and hydrophobic faces) are potent ice growth inhibitors, and that solution-state studies of AFGPs suggest they have a defined hydrophobic face which binds to ice. We show that by synthesising polymers with a sugar on one face, and a hydrophobic opposing face we can selectively introduce the ability to slow ice growth. This is improtant as it shows that the sugar alone is not the essential component but rather the spacial segregation of different units along a polymer backbone.

Read the paper here

Facially Amphipathic Glycopolymers Inhibit Ice Recrystallization

Fri 20 Apr 2018, 08:29 | Tags: Group News, Publication

Responsive Glyco-Particles in ACS MacroLetters

Our latest work, from Sangho, has been published in ACS MacoLetters. This work continues our interest in designing nanomaterials which can mimic the complexity of natural glycans (carbohydrates) for biomedical applications. Most glyco-materials are static- they present the same glycan over time in the same format, but this is not representative of the cell surface. By the action of enzymes, glycans are constantly being presented, modified, recycled and so on. Here we enginnered gold nanoparticle surfaces so that the presentation of lactose could be controlled by temperature. To achieve this we added a responsive polymer 'gate' to the particles, which upon heating collapses (pNIPAM) and then presents the glycan present on another, non-responsive polymer. Using this we were able to probe the lactose-lactose interaction, which is sugested to be a carbohydrate-carbohydrate interaction mediated by divalent ions such as calcium. Whilst the function of CCIs is unclear, we show here that controlling the expression of lactose does let us control lac-lac interactinos, but also lac-GM3 interactions.

Read the paper here

Triggerable multivalent glyconanoparticles for probing carbohydrate-carbohydrate interactions

Mon 22 Jan 2018, 08:39 | Tags: Publication

Antimicrobial Nanoparticles in Biomacromolecules

Antimicrobial resistance to current drugs is an urgent global healthcare threat. New treatments are diagnostics are urgently needed, otherwise a simple cut may lead to serious infections in the future. Traditional small molecules drugs work by targetting a specific enzyme (typically) and requires permeation into the bacteria to function. Antimicrobial peptides are well known as Natures own defense against bacterial infections; these are typically rigid positively charged peptides and there are many reports of using polycations to mimic these. However, these are typically tested against Gram negative bacteria only. In our latest paper we investigate polymer-coated coated nanoparticles for their activity against E.coli and mycobacterium smegmatis, which is a Mycobacteria containing a complex cell wall rich in glycans. We show that multivalent presentation of the polymers on nanoparticles increases the activity (on a per polymer and mass basis) but crucially this increase in actiivty is due to different mechanisms against each strain. Against E.Coli membrane lysis is seen and the particles are bacteriocidal (kills them!). However, against mycobacteria the particles are bacteriostatic (stops them growing) and there is not signficant membrane lysis. This shows that the current assumptions that all polycations function by simple membrane lysis is not correct and that deeper investigations to understand their function is essential.

This work was conducted in collaboration with Dr Elizabeth Fullam's lab at Warwick, who are experts in pathogenic bacteria including Mycobacterium Tuberculosis and follows on from our previous collaborations into new drugs and polymer antibiotics

Read the paper here

Multivalent Antimicrobial Polymer Nanoparticles Target Mycobacteria and Gram-Negative Bacteria by Distinct Mechanisms


Tue 12 Dec 2017, 09:49 | Tags: Group News, Publication

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