ORCID Profile
0000-0003-2312-9803
Current Organisation
University of Western Australia
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Nanomedicine | Nanotechnology | Nanobiotechnology |
Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Technology
Publisher: IEEE
Date: 28-08-2022
Publisher: American Chemical Society (ACS)
Date: 16-07-2020
Publisher: Springer Science and Business Media LLC
Date: 10-12-2020
DOI: 10.1038/S41467-020-20186-0
Abstract: The evolution of gaseous products is a feature common to several electrochemical processes, often resulting in bubbles adhering to the electrode’s surface. Adherent bubbles reduce the electrode active area, and are therefore generally treated as electrochemically inert entities. Here, we show that this general assumption does not hold for gas bubbles masking anodes operating in water. By means of imaging electrochemiluminescent systems, and by studying the anisotropy of polymer growth around bubbles, we demonstrate that gas cavities adhering to an electrode surface initiate the oxidation of water-soluble species more effectively than electrode areas free of bubbles. The corona of a bubble accumulates hydroxide anions, unbalanced by cations, a phenomenon which causes the oxidation of hydroxide ions to hydroxyl radicals to occur at potentials at least 0.7 V below redox tabled values. The downhill shift of the hydroxide oxidation at the corona of the bubble is likely to be a general mechanism involved in the initiation of heterogeneous electrochemical reactions in water, and could be harnessed in chemical synthesis.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.NANO.2019.04.006
Abstract: Triple negative breast cancers (TNBC) are aggressive malignancies for which chemotherapy is the only treatment option. Many TNBC acquire chemotherapy resistance, notably docetaxel, which has been associated with the overexpression of transcription factors (TFs), such as ENGRAILED1 (EN1). Here, we have developed a tumor delivery system for docetaxel-PGMA-PAA-nanoparticles and interference peptides designed to specifically inhibit EN1 (EN1-iPeps). To promote tumor specific targeting, we functionalized these nanoparticles with EN1-iPeps engineered with RGD sequences. We found that these peptides reduce cell viability and induce apoptosis in TNBC cells with negligible effects on normal cells (EN1
Publisher: American Chemical Society (ACS)
Date: 27-10-2011
DOI: 10.1021/NN2022149
Abstract: Polymer nanoparticles are widely used as a highly generalizable tool to entrap a range of different drugs for controlled or site-specific release. However, despite numerous studies examining the kinetics of controlled release, the biological behavior of such nanoparticles remains poorly understood, particularly with respect to endocytosis and intracellular trafficking. We synthesized polyethylenimine-decorated polymer nanospheres (ca. 100-250 nm) of the type commonly used for drug release and used correlated electron microscopy, fluorescence spectroscopy and microscopy, and relaxometry to track endocytosis in neural cells. These capabilities provide insight into how polyethylenimine mediates the entry of nanoparticles into neural cells and show that polymer nanosphere uptake involves three distinct steps, namely, plasma membrane attachment, fluid-phase as well as clathrin- and caveolin-independent endocytosis, and progressive accumulation in membrane-bound intracellular vesicles. These findings provide detailed insight into how the intracellular delivery of nanoparticles is mediated by polyethylenimine, which is presently the most commonly used nonviral gene transfer agent. This fundamental knowledge may also assist in the preparation of next-generation nonviral vectors.
Publisher: American Chemical Society (ACS)
Date: 30-11-2020
DOI: 10.1021/JACS.0C11708
Publisher: Elsevier
Date: 2017
Publisher: Optica Publishing Group
Date: 28-04-2022
DOI: 10.1364/BOE.458478
Abstract: As millimetre wave (MMW) frequencies of the electromagnetic spectrum are increasingly adopted in modern technologies such as mobile communications and networking, characterising the biological effects is critical in determining safe exposure levels. We study the exposure of primary human dermal fibroblasts to MMWs, finding MMWs trigger genomic and transcriptomic alterations. In particular, repeated 60 GHz, 2.6 mW cm −2 , 46.8 J cm −2 d −1 MMW doses induce a unique physiological response after 2 and 4 days exposure. We show that high dose MMWs induce simultaneous non-thermal alterations to the transcriptome and DNA structural dynamics, including formation of G-quadruplex and i-motif secondary structures, but not DNA damage.
Publisher: IEEE
Date: 08-11-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3SC02533K
Abstract: DNA G-quadruplex-stabilising ligands can induce global or specific changes in chromatin accessibility and the transcriptome depending on the targeting specificity of the molecule.
Publisher: CSIRO Publishing
Date: 2020
DOI: 10.1071/CH20071
Abstract: The utility of dendrimers as effective carriers for targeted drug delivery and imaging has been facilitated by a high degree of molecular uniformity, narrow molecular weight distribution, tunable size and shape characteristics, and multivalency. Dendrimer–quantum dot (QD) nanocomposites have traditionally been synthesised by electrostatic self-assembly of preformed dendrimers and QDs, but higher generations are associated with limited flexibility and increased cytotoxicity. In this paper, we report the fabrication of CdTe QD nanoparticles using a dendronised linear copolymer bearing thiolated fourth-generation poly(amido amine) (PAMAM) dendrons as the capping and stabilising agent. We demonstrate this approach enables synthesis of nanocomposites with aqueous and photophysical stability.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9SC01432B
Abstract: This article demonstrates a fully synthetic strategy enabling CRISPR-mediated activation of tumour suppressor genes in vivo to reduce tumour burden.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0NJ03425H
Abstract: Docetaxel (DTX) is a widely used chemotherapy drug that is associated with numerous side effects and limited bioavailability. We show synthetic copolymer conjugates of docetaxel with drug loading up to 20% and assess their efficacy in MCF-7 cells.
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C005022A
Abstract: CePO(4) nanorods decorated with QDs (QDs@CePO(4)) can be prepared in a sequential, aqueous procedure under continuous flow using a rotating tube processor and a narrow channel reactor. The emission from the QD@CePO(4) is tunable from green to red by simply adjusting the feeding rate, which in turn regulates the particle size of the QDs. The Ce(3+) ions in the QDs@CePO(4) serve as an efficient fluorescence resonance energy transfer (FRET) donor, effectively enlarging the Stokes shift of the QDs.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8CC03945C
Abstract: N -Functionalised multicarbazoles were found to be highly selective towards G-quadruplex DNA in the presence of 250× excess duplex DNA competitor.
Publisher: Oxford University Press (OUP)
Date: 04-10-2021
Abstract: Breast cancer is the most commonly diagnosed malignancy in women, and while the survival prognosis of patients with early-stage, non-metastatic disease is ∼75%, recurrence poses a significant risk and advanced and/or metastatic breast cancer is incurable. A distinctive feature of advanced breast cancer is an unstable genome and altered gene expression patterns that result in disease heterogeneity. Transcription factors represent a unique therapeutic opportunity in breast cancer, since they are known regulators of gene expression, including gene expression involved in differentiation and cell death, which are themselves often mutated or dysregulated in cancer. While transcription factors have traditionally been viewed as ‘undruggable’, progress has been made in the development of small-molecule therapeutics to target relevant protein–protein, protein–DNA and enzymatic active sites, with varying levels of success. However, non-traditional approaches such as epigenetic editing, transcriptional control via CRISPR/dCas9 systems, and gene regulation through non-canonical nucleic acid secondary structures represent new directions yet to be fully explored. Here, we discuss these new approaches and current limitations in light of new therapeutic opportunities for breast cancers.
Publisher: Royal Society of Chemistry (RSC)
Date: 2006
DOI: 10.1039/B517131H
Publisher: American Chemical Society (ACS)
Date: 11-03-2021
DOI: 10.1021/JACS.1C00258
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7SC00097A
Abstract: Tools for editing the genome and epigenome have revolutionised the field of molecular biology and represent a new frontier in targeted therapeutic intervention.
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1NR10786K
Abstract: Stabilization of enzymes has become a major focus in the quest to improve the activity, sustainability and recyclability of enzymes for their successful integration into both industry and medicine. Here, we describe the kinetic and thermodynamic stabilization of a variety of enzymes in the presence of cationic multifunctional polymeric nanoparticles.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Springer New York
Date: 2018
DOI: 10.1007/978-1-4939-7774-1_13
Abstract: The potential impact of CRISPR/Cas9, TALE, and zinc finger technology is immense, both with respect to their use as tools for understanding the roles and functions of the genomic elements and epigenome modifications in an endogenous context and as new methods for treatment of diseases. Application of such technologies has drawn attention, however, to the prevailing lack of effective delivery methods. Promising viral and non-viral methods both currently fall short when the efficient delivery of large plasmids or multiple plasmids is required. Therefore, the use of TALE and CRISPR platforms has been severely limited in applications where selection methods to increase the relative proportion of treated cells are not applicable, and it represents a significant bottleneck in the further application of these tools as therapeutics.The protocol presented here describes the synthesis of a dendronized polymer as a highly efficient and nontoxic transfection agent. Furthermore, the optimization of the polymer as a co-transfection reagent for large and multiple plasmids in cell lines is described, in addition to general considerations for co-transfection experiments. Usage of this method has allowed for significantly improved large plasmid co-transfection efficiency over Lipofectamine 2000 in multiple cell lines, allowing an improved delivery of CRISPR/dCas9 and TALE systems.
Publisher: American Chemical Society (ACS)
Date: 30-12-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0CC07115C
Abstract: We present a series of synthetic polymer hydrogels which break the traditional correlation between pore size and mechanical properties.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5NR08331A
Abstract: Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2NJ40016B
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0TC01716G
Abstract: The integration of terahertz frequencies and nanomaterials enables development of technologies to improve generation, detection and sensing applications.
Publisher: Elsevier BV
Date: 2017
Publisher: American Chemical Society (ACS)
Date: 11-09-2023
Publisher: Cold Spring Harbor Laboratory
Date: 23-08-2023
DOI: 10.1101/2023.08.21.554220
Abstract: Cancer is a heterogenous disease, with multiple cellular subpopulations present within a single tumour mass that differ genetically and morphologically, and thus respond differently to chemotherapeutics. Epithelial-to-Mesenchymal transition (EMT) has been shown to play a role in tumour heterogeneity. Single-cell sequencing is critical to identify cell-type-specific transcriptomic differences with multiplexing methods increasing experimental scope with reduced cost. Cell hashing with barcoded antibodies is commonly used to multiplex s les but is limited to s les expressing target antigens. Antigen-independent methods of barcoding cells, such as barcoded lipid-anchors, have gained traction but present substantial populations that cannot be unambiguously demultiplexed. Herein we report a multiplexed single-cell transfection-enabled cell hashing sequencing (scTECH-seq) platform, which uses antigen-independent endocytic uptake to barcode cells, resulting in efficient, uniform barcoding with high cell recovery. We apply this methodology to identify distinct metastable cell states in human mammary cells undergoing EMT and show that stabilisation of G-quadruplex DNA has the potential to inhibit EMT.
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/B925531A
Publisher: Elsevier
Date: 2017
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.BIOCHI.2022.03.001
Abstract: DNA is naturally dynamic and can self-assemble into alternative secondary structures including the intercalated motif (i-motif), a four-stranded structure formed in cytosine-rich DNA sequences. Until recently, i-motifs were thought to be unstable in physiological cellular environments. Studies demonstrating their existence in the human genome and role in gene regulation are now shining light on their biological relevance. Herein, we review the effects of epigenetic modifications on i-motif structure and stability, and biological factors that affect i-motif formation within cells. Furthermore, we highlight recent progress in targeting i-motifs with structure-specific ligands for biotechnology and therapeutic purposes.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2RA21058D
Publisher: American Chemical Society (ACS)
Date: 08-07-2008
DOI: 10.1021/CG800045U
Publisher: American Chemical Society (ACS)
Date: 26-10-2009
DOI: 10.1021/JA9065046
Abstract: Micelles, polyelectrolytes, peptides, and plasmid DNA with well-defined growth cavities can function as templates for the synthesis of metal nanocrystals. In a similar way, carbon-based toroidal 'nanoreactors' composed of clustered fullerenes could be used to synthesize nanohybrids by forming metal nanocrystals within the confines of the ring.
Publisher: Oxford University Press (OUP)
Date: 20-04-2020
DOI: 10.1093/NAR/GKAA262
Abstract: Aberrant KRAS signaling is a driver of many cancers and yet remains an elusive target for drug therapy. The nuclease hypersensitive element of the KRAS promoter has been reported to form secondary DNA structures called G-quadruplexes (G4s) which may play important roles in regulating KRAS expression, and has spurred interest in structural elucidation studies of the KRAS G-quadruplexes. Here, we report the first high-resolution crystal structure (1.6 Å) of a KRAS G-quadruplex as a 5′-head-to-head dimer with extensive poly-A π-stacking interactions observed across the dimer. Molecular dynamics simulations confirmed that the poly-A π-stacking interactions are also maintained in the G4 monomers. Docking and molecular dynamics simulations with two G4 ligands that display high stabilization of the KRAS G4 indicated the poly-A loop was a binding site for these ligands in addition to the 5′-G-tetrad. Given sequence and structural variability in the loop regions provide the opportunity for small-molecule targeting of specific G4s, we envisage this high-resolution crystal structure for the KRAS G-quadruplex will aid in the rational design of ligands to selectively target KRAS.
Publisher: American Chemical Society (ACS)
Date: 28-07-2022
DOI: 10.1021/JACS.2C02793
Abstract: Non-viral delivery is an important strategy for selective and efficient gene therapy, immunization, and RNA interference, which overcomes problems of genotoxicity and inherent immunogenicity associated with viral vectors. Liposomes and polymers are compelling candidates as carriers for intracellular, non-viral delivery, but maximal efficiencies of around 1% have been reported for the most advanced non-viral carriers. Here, we develop a library of dendronized bottlebrush polymers with controlled defects, displaying a level of precision surpassed only by biological molecules like DNA, RNA, and proteins. We test concurrent and competitive delivery of DNA and show for the first time that, while intracellular communication is thought to be an exclusively biomolecular phenomenon, such communication between synthetic macromolecular complexes can also take place. Our findings challenge the assumption that delivery agents behave as bystanders that enable transfection by passive intracellular release of genetic cargo and improve upon coarse strategies in intracellular carrier design lacking control over polymer sequence, architecture, and composition, leading to a hit-or-miss outcome. Understanding the communication that takes place between macromolecules will help improve the design of non-viral delivery agents and facilitate translation of genome engineering, vaccines, and nucleic acid-based therapies.
Publisher: Springer Science and Business Media LLC
Date: 08-10-2018
DOI: 10.1038/S41565-018-0272-2
Abstract: Gold nanorods are one of the most widely explored inorganic materials in nanomedicine for diagnostics, therapeutics and sensing
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1NJ01566D
Abstract: A dendronised polymer functionalised with SP94 targeting peptide achieves highly selective transient transfection of liver cancer cells over normal non-transformed hepatocytes.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.BIOCHI.2021.07.008
Abstract: Paraspeckles are RNA-protein structures within the nucleus of mammalian cells, capable of orchestrating various biochemical processes. An overexpression of the architectural component of paraspeckles, a long non-coding RNA called NEAT1 (Nuclear Enriched Abundant Transcript 1), has been linked to a variety of cancers and is often associated with poor patient prognosis. Thus, there is an accumulating interest in the role of paraspeckles in carcinogenesis, however there is a limited understanding of how NEAT1 expression is regulated. Here, we demonstrate that both nuclear G-quadruplex (G4) and paraspeckle formation are significantly increased in a human breast cancer cell line compared to non-tumorigenic breast cells. Moreover, we identified and characterized G4-forming sequences within the NEAT1 promoter and demonstrate stabilization of G4 DNA with a G4-stabilizing small molecule results in a significant alteration in both paraspeckle formation and NEAT1 expression. This G4-mediated alteration of NEAT1 at both the transcriptional and post-transcriptional levels was evident in U2OS osteosarcoma cells, MCF-7 breast adenocarcinoma and MDA-MB-231 triple negative breast cancer cells.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9RA03518D
Abstract: The development of efficient non-viral transfection agents capable of delivering multiple nucleic acids is crucial for the field of genome engineering. Herein a facile methodology of polyplex labelling and tracking with quantum dots is presented.
Publisher: Wiley
Date: 13-03-2012
Abstract: The use of nanoparticles for targeted delivery of therapeutic agents to sites of injury or disease in the central nervous system (CNS) holds great promise. However, the biodistribution of nanoparticles following in vivo administration is often unknown, and concerns have been raised regarding potential toxicity. Using poly(glycidyl methacrylate) (PGMA) nanoparticles coated with polyethylenimine (PEI) and containing superparamagnetic iron oxide nanoparticles as a magnetic resonance imaging (MRI) contrast agent and rhodamine B as a fluorophore, whole animal MRI and fluorescence analyses are used to demonstrate that these nanoparticles (NP) remain close to the site of injection into a partial injury of the optic nerve, a CNS white matter tract. In addition, some of these NP enter axons and are transported to parent neuronal somata. NP also remain in the eye following intravitreal injection, a non-injury model. Considerable infiltration of activated microglia/macrophages occurs in both models. Using magnetic concentration and fluorescence visualization of tissue homogenates, no dissemination of the NP into peripheral tissues is observed. Histopathological analysis reveals no toxicity in organs other than at the injection sites. Multifunctional nanoparticles may be a useful mechanism to deliver therapeutic agents to the injury site and somata of injured CNS neurons and thus may be of therapeutic value following brain or spinal cord trauma.
Publisher: Future Medicine Ltd
Date: 04-2016
DOI: 10.2217/NNM.16.7
Abstract: Treatment of acute cardiac ischemia remains an area in which there are opportunities for therapeutic improvement. Despite significant advances, many patients still progress to cardiac hypertrophy and heart failure. Timely reperfusion is critical in rescuing vulnerable ischemic tissue and is directly related to patient outcome, but reperfusion of the ischemic myocardium also contributes to damage. Overproduction of reactive oxygen species, initiation of an inflammatory response and deregulation of calcium homeostasis all contribute to injury, and difficulties in delivering a sufficient quantity of drug to the affected tissue in a controlled manner is a limitation of current therapies. Nanotechnology may offer significant improvements in this respect. Here, we review recent ex les of how nanoparticles can be used to improve delivery to the ischemic myocardium, and suggest some approaches that may lead to improved therapies for acute cardiac ischemia.
Location: United States of America
Start Date: 2023
End Date: 2024
Funder: Western Australian Future Health and Innovation Fund, Government of Western Australia
View Funded ActivityStart Date: 2022
End Date: 2023
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2022
End Date: 2024
Funder: Australian Research Council
View Funded ActivityStart Date: 2008
End Date: 2011
Funder: Australian Government
View Funded ActivityStart Date: 09-2022
End Date: 08-2025
Amount: $510,000.00
Funder: Australian Research Council
View Funded Activity