Publications
38 results found
Najer A, Rifaie Graham O, Yeow J, et al., 2023, Differences in human plasma protein interactions between various polymersomes and stealth liposomes as observed by fluorescence correlation spectroscopy, Macromolecular Bioscience, Vol: 23, ISSN: 1616-5187
A significant factor hindering the clinical translation of polymersomes as vesicular nanocarriers is the limited availability of comparative studies detailing their interaction with blood plasma proteins compared to liposomes. Here, polymersomes are self-assembled via film rehydration, solvent exchange, and polymerization-induced self-assembly using five different block copolymers. The hydrophilic blocks are composed of anti-fouling polymers, poly(ethylene glycol) (PEG) or poly(2-methyl-2-oxazoline) (PMOXA), and all the data is benchmarked to PEGylated “stealth” liposomes. High colloidal stability in human plasma (HP) is confirmed for all but two tested nanovesicles. In situ fluorescence correlation spectroscopy measurements are then performed after incubating unlabeled nanovesicles with fluorescently labeled HP or the specific labeled plasma proteins, human serum albumin, and clusterin (apolipoprotein J). The binding of HP to PMOXA-polymersomes could explain their relatively short circulation times found previously. In contrast, PEGylated liposomes also interact with HP but accumulate high levels of clusterin, providing them with their known prolonged circulation time. The absence of significant protein binding for most PEG-polymersomes indicates mechanistic differences in protein interactions and associated downstream effects, such as cell uptake and circulation time, compared to PEGylated liposomes. These are key observations for bringing polymersomes closer to clinical translation and highlighting the importance of such comparative studies.
Lee J, Mulay P, Tamasi MJ, et al., 2023, A fully automated platform for photoinitiated RAFT polymerization, Digital Discovery, Vol: 2, Pages: 219-233, ISSN: 2635-098X
Oxygen tolerant polymerizations including Photoinduced Electron/Energy Transfer-Reversible Addition–Fragmentation Chain-Transfer (PET-RAFT) polymerization allow for high-throughput synthesis of diverse polymer architectures on the benchtop in parallel. Recent developments have further increased throughput using liquid handling robotics to automate reagent handling and dispensing into well plates thus enabling the combinatorial synthesis of large polymer libraries. Although liquid handling robotics can enable automated polymer reagent dispensing in well plates, photoinitiation and reaction monitoring require automation to provide a platform that enables the reliable and robust synthesis of various polymer compositions in high-throughput where polymers with desired molecular weights and low dispersity are obtained. Here, we describe the development of a robotic platform to fully automate PET-RAFT polymerizations and provide individual control of reactions performed in well plates. On our platform, reagents are automatically dispensed in well plates, photoinitiated in individual wells with a custom-designed lightbox until the polymerizations are complete, and monitored online in real-time by tracking fluorescence intensities on a fluorescence plate reader, with well plate transfers between instruments occurring via a robotic arm. We found that this platform enabled robust parallel polymer synthesis of both acrylate and acrylamide homopolymers and copolymers, with high monomer conversions and low dispersity. The successful polymerizations obtained on this platform make it an efficient tool for combinatorial polymer chemistry. In addition, with the inclusion of machine learning protocols to help navigate the polymer space towards specific properties of interest, this robotic platform can ultimately become a self-driving lab that can dispense, synthesize, and monitor large polymer libraries.
Rifaie Graham O, Yeow J, Najer A, et al., 2022, Photoswitchable gating of non-equilibrium enzymatic feedback in chemically communicating polymersome nanoreactors, Nature Chemistry, Vol: 15, Pages: 110-118, ISSN: 1755-4330
The circadian rhythm generates out-of-equilibrium metabolite oscillations controlled by feedbackloops under light/dark cycles. Here we describe a non-equilibrium nanosystem comprising a binarypopulation of enzyme-containing polymersomes capable of light-gated chemical communication,controllable feedback and coupling to macroscopic oscillations. The populations consist of esterase-containing polymersomes functionalised with photo-responsive Donor-Acceptor Stenhouse Adducts(DASA) and light-insensitive semi-permeable urease-loaded polymersomes. The DASA-polymersomemembrane becomes permeable under green light, switching on esterase activity and decreasing thepH, which in turn initiates production of alkali in the urease-containing population. A pH-sensitivepigment that absorbs green light when protonated provides a negative feedback loop for deactivatingthe DASA-polymersomes. Simultaneously, increased alkali production deprotonates the pigment, re-activating esterase activity by opening the membrane gate. We utilise light-mediated fluctuations ofpH to perform non-equilibrium communication between the nanoreactors and use the feedback loopsto induce work as chemomechanical swelling/deswelling oscillations in a crosslinked hydrogel. Weenvision possible applications in artificial organelles, protocells, and soft robotics.
Najer A, Blight J, Ducker CB, et al., 2022, Potent virustatic polymer-lipid nanomimics block viral entry and inhibit malaria parasites in vivo, ACS Central Science, Vol: 8, Pages: 1238-1257, ISSN: 2374-7943
Infectious diseases continue to pose a substantial burden on global populations, requiring innovative broad-spectrum prophylactic and treatment alternatives. Here, we have designed modular synthetic polymer nanoparticles that mimic functional components of host cell membranes, yielding multivalent nanomimics that act by directly binding to varied pathogens. Nanomimic blood circulation time was prolonged by reformulating polymer–lipid hybrids. Femtomolar concentrations of the polymer nanomimics were sufficient to inhibit herpes simplex virus type 2 (HSV-2) entry into epithelial cells, while higher doses were needed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given their observed virustatic mode of action, the nanomimics were also tested with malaria parasite blood-stage merozoites, which lose their invasive capacity after a few minutes. Efficient inhibition of merozoite invasion of red blood cells was demonstrated both in vitro and in vivo using a preclinical rodent malaria model. We envision these nanomimics forming an adaptable platform for developing pathogen entry inhibitors and as immunomodulators, wherein nanomimic-inhibited pathogens can be secondarily targeted to sites of immune recognition.
Kim H, Yeow J, Najer A, et al., 2022, Microliter scale synthesis of luciferase-encapsulated polymersomes as artificial organelles for optogenetic modulation of cardiomyocyte beating, Advanced Science, Vol: 9, Pages: 1-12, ISSN: 2198-3844
Constructing artificial systems that effectively replace or supplement natural biological machinery within cells is one of the fundamental challenges underpinning bioengineering. At the sub-cellular scale, artificial organelles (AOs) have significant potential as long-acting biomedical implants, mimicking native organelles by conducting intracellularly compartmentalized enzymatic actions. The potency of these AOs can be heightened when judiciously combined with genetic engineering, producing highly tailorable biohybrid cellular systems. Here, the authors present a cost-effective, microliter scale (10 µL) polymersome (PSome) synthesis based on polymerization-induced self-assembly for the in situ encapsulation of Gaussia luciferase (GLuc), as a model luminescent enzyme. These GLuc-loaded PSomes present ideal features of AOs including enhanced enzymatic resistance to thermal, proteolytic, and intracellular stresses. To demonstrate their biomodulation potential, the intracellular luminescence of GLuc-loaded PSomes is coupled to optogenetically engineered cardiomyocytes, allowing modulation of cardiac beating frequency through treatment with coelenterazine (CTZ) as the substrate for GLuc. The long-term intracellular stability of the luminescent AOs allows this cardiostimulatory phenomenon to be reinitiated with fresh CTZ even after 7 days in culture. This synergistic combination of organelle-mimicking synthetic materials with genetic engineering is therefore envisioned as a highly universal strategy for the generation of new biohybrid cellular systems displaying unique triggerable properties.
McKay PF, Zhou J, Frise R, et al., 2022, Polymer formulated self-amplifying RNA vaccine is partially protective against influenza virus infection in ferrets, Oxford Open Immunology, Vol: 3, ISSN: 2633-6960
COVID-19 has demonstrated the power of RNA vaccines as part of a pandemic response toolkit. Another virus with pandemic potential is influenza. Further development of RNA vaccines in advance of a future influenza pandemic will save time and lives. As RNA vaccines require formulation to enter cells and induce antigen expression, the aim of this study was to investigate the impact of a recently developed bioreducible cationic polymer, pABOL for the delivery of a self-amplifying RNA (saRNA) vaccine for seasonal influenza virus in mice and ferrets. Mice and ferrets were immunized with pABOL formulated saRNA vaccines expressing either haemagglutinin (HA) from H1N1 or H3N2 influenza virus in a prime boost regime. Antibody responses, both binding and functional were measured in serum after immunization. Animals were then challenged with a matched influenza virus either directly by intranasal inoculation or in a contact transmission model. While highly immunogenic in mice, pABOL-formulated saRNA led to variable responses in ferrets. Animals that responded to the vaccine with higher levels of influenza virus-specific neutralizing antibodies were more protected against influenza virus infection. pABOL-formulated saRNA is immunogenic in ferrets, but further optimization of RNA vaccine formulation and constructs is required to increase the quality and quantity of the antibody response to the vaccine.
Blakney AK, McKay PF, Hu K, et al., 2021, Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines, Journal of Controlled Release, Vol: 338, Pages: 201-210, ISSN: 0168-3659
Self-amplifying RNA (saRNA) is a next-generation vaccine platform, but like all nucleic acids, requires a delivery vehicle to promote cellular uptake and protect the saRNA from degradation. To date, delivery platforms for saRNA have included lipid nanoparticles (LNP), polyplexes and cationic nanoemulsions; of these LNP are the most clinically advanced with the recent FDA approval of COVID-19 based-modified mRNA vaccines. While the effect of RNA on vaccine immunogenicity is well studied, the role of biomaterials in saRNA vaccine effectiveness is under investigated. Here, we tested saRNA formulated with either pABOL, a bioreducible polymer, or LNP, and characterized the protein expression and vaccine immunogenicity of both platforms. We observed that pABOL-formulated saRNA resulted in a higher magnitude of protein expression, but that the LNP formulations were overall more immunogenic. Furthermore, we observed that both the helper phospholipid and route of administration (intramuscular versus intranasal) of LNP impacted the vaccine immunogenicity of two model antigens (influenza hemagglutinin and SARS-CoV-2 spike protein). We observed that LNP administered intramuscularly, but not pABOL or LNP administered intranasally, resulted in increased acute interleukin-6 expression after vaccination. Overall, these results indicate that delivery systems and routes of administration may fulfill different delivery niches within the field of saRNA genetic medicines.
Ng G, Li M, Yeow J, et al., 2020, Benchtop Preparation of Polymer Brushes by SI-PET-RAFT: The Effect of the Polymer Composition and Structure on Inhibition of a <i>Pseudomonas</i> Biofilm, ACS APPLIED MATERIALS & INTERFACES, Vol: 12, Pages: 55243-55254, ISSN: 1944-8244
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- Citations: 35
Gurnani P, Blakney AK, Yeow J, et al., 2020, An improved synthesis of poly(amidoamine)s for complexation with self-amplifying RNA and effective transfection, Polymer Chemistry, Vol: 11, Pages: 5861-5869, ISSN: 1759-9954
Cationic polymers are widely used as materials to condense nucleic acids for gene-based therapies. These have been developed to mainly deliver DNA and RNA for cancer therapies but the ongoing COVID-19 pandemic has demonstrated an urgent need for new DNA and RNA vaccines. Given this, suitable manufacturing conditions for such cationic polymers which can protect the nucleic acid in the formulation and delivery stages but release the cargo in the correct cellular compartment effectively and safely are required. A number of polymers based on poly(amidoamine)s fit these criteria but their syntheses can be time-consuming, inefficient and poorly reproducible, precluding their adoption as manufacturable vaccine excipients. Here we report an improved synthesis of poly(cystamine bisacrylamide-co-4-amino-1-butanol), abbreviated as pABOL, via modifications in concentration, reaction time and reaction conditions. Optimisation of monomer contents and stoichiometries, solvents, diluents and temperature, combined with the application of microwaves, enabled the preparation of vaccine candidate pABOL materials in 4 h compared to 48 h reported for previous syntheses. These procedures were highly reproducible in multiple repeat syntheses. Transfection experiments with a model RNA showed that polymers of formulation with appropriate molar masses and mass distributions were as effective in model cell lines as polymers derived from the unoptimised syntheses which have been shown to have high efficacy as RNA vaccine formulation candidates.
Blakney AK, Zhu Y, McKay PF, et al., 2020, Big is beautiful: enhanced saRNA delivery and immunogenicity by a higher molecular weight, bioreducible, cationic polymer, ACS Nano, Vol: 14, Pages: 5711-5727, ISSN: 1936-0851
Self-amplifying RNA (saRNA) vaccines are highly advantageous, as they result in enhanced protein expression compared to mRNA (mRNA), thus minimizing the required dose. However, previous delivery strategies were optimized for siRNA or mRNA and do not necessarily deliver saRNA efficiently due to structural differences of these RNAs, thus motivating the development of saRNA delivery platforms. Here, we engineer a bioreducible, linear, cationic polymer called “pABOL” for saRNA delivery and show that increasing its molecular weight enhances delivery both in vitro and in vivo. We demonstrate that pABOL enhances protein expression and cellular uptake via both intramuscular and intradermal injection compared to commercially available polymers in vivo and that intramuscular injection confers complete protection against influenza challenge. Due to the scalability of polymer synthesis and ease of formulation preparation, we anticipate that this polymer is highly clinically translatable as a delivery vehicle for saRNA for both vaccines and therapeutics.
Xu S, Zhang T, Kuchel RP, et al., 2020, Gradient Polymerization-Induced Self-Assembly: A One-Step Approach, MACROMOLECULAR RAPID COMMUNICATIONS, Vol: 41, ISSN: 1022-1336
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- Citations: 19
Zhang T, Yeow J, Boyer C, 2019, A cocktail of vitamins for aqueous RAFT polymerization in an open-to-air microtiter plate, POLYMER CHEMISTRY, Vol: 10, Pages: 4643-4654, ISSN: 1759-9954
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- Citations: 40
Penfold NJW, Yeow J, Boyer C, et al., 2019, Emerging Trends in Polymerization-Induced Self-Assembly, ACS MACRO LETTERS, Vol: 8, Pages: 1029-1054
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- Citations: 360
Zaquen N, Azizi WAAW, Yeow J, et al., 2019, Alcohol-based PISA in batch and flow: exploring the role of photoinitiators, POLYMER CHEMISTRY, Vol: 10, Pages: 2406-2414, ISSN: 1759-9954
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- Citations: 39
Corrigan N, Yeow J, Judzewitsch P, et al., 2019, Seeing the Light: Advancing Materials Chemistry through Photopolymerization, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 58, Pages: 5170-5189, ISSN: 1433-7851
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- Citations: 355
Xu S, Yeow J, Boyer C, 2018, Exploiting Wavelength Orthogonality for Successive Photoinduced Polymerization-Induced Self-Assembly and Photo-Crosslinking, ACS MACRO LETTERS, Vol: 7, Pages: 1376-+
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- Citations: 73
Ng G, Yeow J, Chapman R, et al., 2018, Pushing the Limits of High Throughput PET-RAFT Polymerization, MACROMOLECULES, Vol: 51, Pages: 7600-7607, ISSN: 0024-9297
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- Citations: 74
Yeow J, Joshi S, Chapman R, et al., 2018, A Self-Reporting Photocatalyst for Online Fluorescence Monitoring of High Throughput RAFT Polymerization, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 57, Pages: 10102-10106, ISSN: 1433-7851
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- Citations: 42
Zaquen N, Yeow J, Junkers T, et al., 2018, Visible Light-Mediated Polymerization-Induced Self-Assembly Using Continuous Flow Reactors, MACROMOLECULES, Vol: 51, Pages: 5165-5172, ISSN: 0024-9297
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- Citations: 88
Corrigan N, Manahan R, Lew ZT, et al., 2018, Copolymers with Controlled Molecular Weight Distributions and Compositional Gradients through Flow Polymerization, MACROMOLECULES, Vol: 51, Pages: 4553-4563, ISSN: 0024-9297
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- Citations: 84
Yeow J, Chapman R, Gormley AJ, et al., 2018, Up in the air: oxygen tolerance in controlled/living radical polymerisation, CHEMICAL SOCIETY REVIEWS, Vol: 47, Pages: 4357-4387, ISSN: 0306-0012
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- Citations: 277
Namivandi-Zangeneh R, Kwan RJ, Thuy-Khanh N, et al., 2018, The effects of polymer topology and chain length on the antimicrobial activity and hemocompatibility of amphiphilic ternary copolymers, POLYMER CHEMISTRY, Vol: 9, Pages: 1735-1744, ISSN: 1759-9954
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- Citations: 52
Namivandi-Zangeneh R, Kwan RJ, Thuy-Khanh N, et al., 2018, The effects of polymer topology and chain length on the antimicrobial activity and hemocompatibility of amphiphilic ternary copolymers (vol 9, pg 1735, 2017), POLYMER CHEMISTRY, Vol: 9, Pages: 1745-1745, ISSN: 1759-9954
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- Citations: 2
Gormley AJ, Yeow J, Ng G, et al., 2018, An Oxygen-Tolerant PET-RAFT Polymerization for Screening Structure-Activity Relationships, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 57, Pages: 1557-1562, ISSN: 1433-7851
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- Citations: 132
Sadrearhami Z, Yeow J, Thuy-Khanh N, et al., 2017, Biofilm dispersal using nitric oxide loaded nanoparticles fabricated by photo-PISA: influence of morphology, CHEMICAL COMMUNICATIONS, Vol: 53, Pages: 12894-12897, ISSN: 1359-7345
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- Citations: 42
Xu S, Ng G, Xu J, et al., 2017, 2-(Methylthio)ethyl Methacrylate: A Versatile Monomer for Stimuli Responsiveness and Polymerization-Induced Self-Assembly in the Presence of Air, ACS MACRO LETTERS, Vol: 6, Pages: 1237-1244
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- Citations: 88
Yeow J, Chapman R, Xu J, et al., 2017, Oxygen tolerant photopolymerization for ultralow volumes, POLYMER CHEMISTRY, Vol: 8, Pages: 5012-5022, ISSN: 1759-9954
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- Citations: 168
Yeow J, Boyer C, 2017, Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA): New Insights and Opportunities, ADVANCED SCIENCE, Vol: 4
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- Citations: 269
Ng G, Yeow J, Xu J, et al., 2017, Application of oxygen tolerant PET-RAFT to polymerization-induced self-assembly, POLYMER CHEMISTRY, Vol: 8, Pages: 2841-2851, ISSN: 1759-9954
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- Citations: 128
Hinde E, Thammasiraphop K, Duong HTT, et al., 2017, Pair correlation rnicroscopy reveals the role of nanoparticle shape in intracellular transport and site of drug release, NATURE NANOTECHNOLOGY, Vol: 12, Pages: 81-89, ISSN: 1748-3387
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- Citations: 252
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