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Neurosurgical application of olaparib from a thermo-responsive paste potentiates DNA damage to prolong survival in malignant glioma (2024)
Journal Article
Serra, R., Smith, S. J., Rowlinson, J., Gorelick, N., Moloney, C., McCrorie, P., Veal, G. J., Berry, P., Chalmers, A. J., Suk, I., Shakesheff, K. M., Alexander, C., Grundy, R. G., Brem, H., Tyler, B. M., & Rahman, R. (2024). Neurosurgical application of olaparib from a thermo-responsive paste potentiates DNA damage to prolong survival in malignant glioma. British Journal of Cancer, https://doi.org/10.1038/s41416-024-02878-2

Background: There is increased pan-cancer specific interest in repurposing the poly adenosine diphosphate-ribose polymerase-1 (PARP-1) inhibitor, olaparib, for newly diagnosed or recurrent isocitrate dehydrogenase wild type glioblastoma. We explore w... Read More about Neurosurgical application of olaparib from a thermo-responsive paste potentiates DNA damage to prolong survival in malignant glioma.

Discovery and Computational Modelling of Adsorbent Polymers that Effectively Immobilize SARS-CoV-2 with Potential Practical Applications (2024)
Journal Article
Xue, X., Duncan, J. D., Coleman, C. M., Contreas, L., Blackburn, C., Vivero-Lopez, M., Williams, P. M., Ball, J. K., Alexander, C., & Alexander, M. R. (2024). Discovery and Computational Modelling of Adsorbent Polymers that Effectively Immobilize SARS-CoV-2 with Potential Practical Applications. Cell Reports Physical Science, 5(9), Article 102204. https://doi.org/10.1016/j.xcrp.2024.102204

Viral translocation is considered a common way for respiratory viruses to spread and contaminate the surrounding environment. Thus, the discovery of non-eluting polymers that immobilize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upo... Read More about Discovery and Computational Modelling of Adsorbent Polymers that Effectively Immobilize SARS-CoV-2 with Potential Practical Applications.

Supramolecular hydrogels enable co-delivery of chemotherapeutics with synergistic efficacy against patient-derived glioblastoma cells and spheroids (2024)
Journal Article
Cavanagh, R. J., Baquain, S., Alexander, C., Scherman, O. A., & Rahman, R. (2024). Supramolecular hydrogels enable co-delivery of chemotherapeutics with synergistic efficacy against patient-derived glioblastoma cells and spheroids. RSC Advances, https://doi.org/10.1039/D4PM00177J

Drug combinations have been shown to be highly effective in many cancer therapies but the ratios of the individual drugs must be adjusted carefully and formulated appropriately to ensure synergistic action. Here we assessed combinations of doxorubici... Read More about Supramolecular hydrogels enable co-delivery of chemotherapeutics with synergistic efficacy against patient-derived glioblastoma cells and spheroids.

Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine (2024)
Journal Article
Bayraktutan, H., Symonds, P., Brentville, V. A., Moloney, C., Galley, C., Bennett, C. L., Mata, A., Durrant, L., Alexander, C., & Gurnani, P. (2024). Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine. Biomaterials, 311, Article 122647. https://doi.org/10.1016/j.biomaterials.2024.122647

DNA technology has emerged as a promising route to accelerated manufacture of sequence agnostic vaccines. For activity, DNA vaccines must be protected and delivered to the correct antigen presenting cells. However, the physicochemical properties of t... Read More about Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine.

Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms (2024)
Journal Article
Kasza, K., Soukarieh, F., Romero, M., Hardie, K. R., Gurnani, P., Cámara, M., & Alexander, C. (2024). Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms. RSC Applied Polymers, 2(3), 444-455. https://doi.org/10.1039/D3LP00208J

Antimicrobial resistance is a threat to public health for which new treatments are urgently required. The capability of bacteria to form biofilms is of particular concern as it enables high bacterial tolerance to conventional therapies by reducing dr... Read More about Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms.

Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models (2024)
Journal Article
Cavanagh, R. J., Monteiro, P. F., Moloney, C., Travanut, A., Mehradnia, F., Taresco, V., …Alexander, C. (2024). Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models. Biomaterials Science, 12(7), 1822-1840. https://doi.org/10.1039/d3bm01931d

Combinations of the topoisomerase II inhibitor doxorubicin and the poly (ADP-ribose) polymerase inhibitor olaparib offer potential drug-drug synergy for the treatment of triple negative breast cancers (TNBC). In this study we performed in vitro scree... Read More about Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models.

Ciprofloxacin poly(β-amino ester) conjugates enhance antibiofilm activity and slow the development of resistance (2024)
Journal Article
Kasza, K., Richards, B., Jones, S., Romero, M., Robertson, S. N., Hardie, K. R., …Alexander, C. (2024). Ciprofloxacin poly(β-amino ester) conjugates enhance antibiofilm activity and slow the development of resistance. ACS Applied Materials and Interfaces, 16(5), 5412-5425. https://doi.org/10.1021/acsami.3c14357

To tackle the emerging antibiotic resistance crisis, novel antimicrobial approaches are urgently needed. Bacterial biofilms are a particular concern in this context as they are responsible for over 80% of bacterial infections and are inherently more... Read More about Ciprofloxacin poly(β-amino ester) conjugates enhance antibiofilm activity and slow the development of resistance.

Synthetic macromolecular peptide-mimetics with amino acid substructure residues as protein stabilising excipients (2023)
Journal Article
Foralosso, R., Kopiasz, R. J., Mantovani, G., Stolnik, S., & Alexander, C. (2024). Synthetic macromolecular peptide-mimetics with amino acid substructure residues as protein stabilising excipients. Journal of Materials Chemistry B, 12, 1022-1030. https://doi.org/10.1039/d3tb02102e

The clinical use of protein and peptide biotherapeutics requires fabrication of stable products. This particularly concerns stability towards aggregation of proteins or peptides. Here, we tested a hypothesis that interactions between a synthetic pept... Read More about Synthetic macromolecular peptide-mimetics with amino acid substructure residues as protein stabilising excipients.

Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers (2023)
Journal Article
Moloney, C., Mehradnia, F., Cavanagh, R. J., Ibrahim, A., Pearce, A. K., Ritchie, A. A., …Alexander, C. (2023). Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers. Biomaterials Science, 11, 6545-6560. https://doi.org/10.1039/d3bm00609c

The therapeutic efficacy of nanomedicines is highly dependent on their access to target sites in the body, and this in turn is markedly affected by their size, shape and transport properties in tissue. Although there have been many studies in this ar... Read More about Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers.

Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells (2023)
Journal Article
Ogrodzinski, L., Platt, S., Goulding, J., Alexander, C., Farr, T. D., Woolard, J., …Kilpatrick, L. E. (2023). Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells. iScience, 26(7), Article 107232. https://doi.org/10.1016/j.isci.2023.107232

E-selectin is expressed on endothelial cells in response to inflammatory cytokines and mediates leukocyte rolling and extravasation. However, studies have been hampered by lack of experimental approaches to monitor expression in real time in living c... Read More about Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells.

OptoRheo: Simultaneous in situ micro-mechanical sensing and imaging of live 3D biological systems (2023)
Journal Article
Mendonca, T., Lis-Slimak, K., Matheson, A. B., Smith, M. G., Anane-Adjei, A. B., Ashworth, J. C., …Wright, A. J. (2023). OptoRheo: Simultaneous in situ micro-mechanical sensing and imaging of live 3D biological systems. Communications Biology, 6, Article 463. https://doi.org/10.1038/s42003-023-04780-8

Biomechanical cues from the extracellular matrix (ECM) are essential for directing many cellular processes, from normal development and repair, to disease progression. To better understand cell-matrix interactions, we have developed a new instrument... Read More about OptoRheo: Simultaneous in situ micro-mechanical sensing and imaging of live 3D biological systems.

Design of Quorum Sensing Inhibitor–Polymer Conjugates to Penetrate Pseudomonas aeruginosa Biofilms (2023)
Journal Article
Soukarieh, F., Gurnani, P., Romero, M., Halliday, N., Stocks, M., Alexander, C., & Cámara, M. (2023). Design of Quorum Sensing Inhibitor–Polymer Conjugates to Penetrate Pseudomonas aeruginosa Biofilms. ACS Macro Letters, 12(3), 314-319. https://doi.org/10.1021/acsmacrolett.2c00699

Antimicrobial resistance (AMR) is a global threat to public health with a forecast of a negative financial impact of one trillion dollars per annum, hence novel therapeutics are urgently needed. The resistance of many bacteria against current drugs i... Read More about Design of Quorum Sensing Inhibitor–Polymer Conjugates to Penetrate Pseudomonas aeruginosa Biofilms.

OptoRheo: Simultaneous in situ micro-mechanical sensing and 3D imaging of live cell cultures (2023)
Preprint / Working Paper
Mendonca, T., Lis-Slimak, K., Matheson, A. B., Smith, M. G., Anane-Adjei, A. B., Cavanagh, R., …Wright, A. J. OptoRheo: Simultaneous in situ micro-mechanical sensing and 3D imaging of live cell cultures

Biomechanical cues from the extracellular matrix (ECM) are essential for directing many cellular processes, from normal development and repair, to disease progression. To better understand cell-matrix interactions, we have developed a new instrument... Read More about OptoRheo: Simultaneous in situ micro-mechanical sensing and 3D imaging of live cell cultures.

Oxidation of Monoterpenes to Form Diols and Triols: A Versatile Toolbox for Polymer Synthesis (2023)
Journal Article
Fowler, H. R., O'Brien, D. M., Keddie, D. J., Alexander, C., Irvine, D. J., Stockman, R. A., …Taresco, V. (2023). Oxidation of Monoterpenes to Form Diols and Triols: A Versatile Toolbox for Polymer Synthesis. Macromolecular Chemistry and Physics, 224(8), Article 2200446. https://doi.org/10.1002/macp.202200446

Polyols and polyacrylates have a wide range of applications in polymer synthesis as monomers, initiators, or building blocks in a variety of polymerization reaction types. With an ever-growing need to reduce the global dependency on fossil fuels, fin... Read More about Oxidation of Monoterpenes to Form Diols and Triols: A Versatile Toolbox for Polymer Synthesis.

Histopathological impact of Redox-responsive methacrylamide based micellar nanoparticles on Orthotopic Models of Triple Negative Breast Cancers (2022)
Journal Article
Mehradnia, F., Moloney, C., Cavanagh, R., Pearce, A. K., Ritchie, A., Clarke, P., …Alexander, C. (2022). Histopathological impact of Redox-responsive methacrylamide based micellar nanoparticles on Orthotopic Models of Triple Negative Breast Cancers. British Journal of Pharmacy, 7(2), https://doi.org/10.5920/bjpharm.1173

The therapeutic efficacy of anticancer nanocarriers ishighly dependent on their size, shape, targeting ability, and stimuli-responsiveness. Herein, we studied the in vivo therapeutic efficacy ofDoxorubicin (Dox) loaded redox responsive micellar-like... Read More about Histopathological impact of Redox-responsive methacrylamide based micellar nanoparticles on Orthotopic Models of Triple Negative Breast Cancers.

The effect of Amine modification on siRNA delivery of redox-responsive PEGylated amphiphilic micellar nanoparticles for triple negative breast cancer therapy (2022)
Journal Article
Mehradnia, F., & Alexander, C. (2022). The effect of Amine modification on siRNA delivery of redox-responsive PEGylated amphiphilic micellar nanoparticles for triple negative breast cancer therapy. British Journal of Pharmacy, 7(2), https://doi.org/10.5920/bjpharm.1119

We developed a set of methoxypoly(ethyleneglycol)-co-poly(N3-ε-caprolactone) (mPEG-N3PCL)copolymers with different types of amine linkers and investigated thecontribution of the introduced amino linker to the gene delivery efficiency ofnanoparticles.... Read More about The effect of Amine modification on siRNA delivery of redox-responsive PEGylated amphiphilic micellar nanoparticles for triple negative breast cancer therapy.

Evaluation of the relative potential for contact and doffing transmission of SARS-CoV-2 by a range of personal protective equipment materials (2022)
Journal Article
Xue, X., Coleman, C. M., Duncan, J. D., Hook, A. L., Ball, J. K., Alexander, C., & Alexander, M. R. (2022). Evaluation of the relative potential for contact and doffing transmission of SARS-CoV-2 by a range of personal protective equipment materials. Scientific Reports, 12(1), Article 16654. https://doi.org/10.1038/s41598-022-20952-8

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—the causative agent of coronavirus disease 2019 (COVID-19)—has caused a global public health emergency. Personal protective equipment (PPE) is the primary defence against viral exposure in... Read More about Evaluation of the relative potential for contact and doffing transmission of SARS-CoV-2 by a range of personal protective equipment materials.

Metabolic Signatures of Surface-Modified Poly(lactic- co-glycolic acid) Nanoparticles in Differentiated THP-1 Cells Derived with Liquid Chromatography-Mass Spectrometry-based Metabolomics (2022)
Journal Article
Al-Natour, M. A., Abdelrazig, S., Ghaemmaghami, A. M., Alexander, C., & Kim, D. H. (2022). Metabolic Signatures of Surface-Modified Poly(lactic- co-glycolic acid) Nanoparticles in Differentiated THP-1 Cells Derived with Liquid Chromatography-Mass Spectrometry-based Metabolomics. ACS Omega, https://doi.org/10.1021/acsomega.2c01660

Polymeric nanoparticles (NPs) are widely used in preclinical drug delivery investigations, and some formulations are now in the clinic. However, the detailed effects of many NPs at the subcellular level have not been fully investigated. In this study... Read More about Metabolic Signatures of Surface-Modified Poly(lactic- co-glycolic acid) Nanoparticles in Differentiated THP-1 Cells Derived with Liquid Chromatography-Mass Spectrometry-based Metabolomics.

Oxygen-Tolerant RAFT Polymerization Initiated by Living Bacteria (2022)
Journal Article
Bennett, M. R., Moloney, C., Catrambone, F., Turco, F., Myers, B., Kovacs, K., …Gurnani, P. (2022). Oxygen-Tolerant RAFT Polymerization Initiated by Living Bacteria. ACS Macro Letters, 11(8), 954-960. https://doi.org/10.1021/acsmacrolett.2c00372

Living organisms can synthesize a wide range of macromolecules from a small set of natural building blocks, yet there is potential for even greater materials diversity by exploiting biochemical processes to convert unnatural feedstocks into new abiot... Read More about Oxygen-Tolerant RAFT Polymerization Initiated by Living Bacteria.