ORCID Profile
0000-0002-4100-3131
Current Organisation
University of Queensland
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Nanotechnology | Macromolecular and Materials Chemistry | Nanobiotechnology | Nanomedicine | Synthesis Of Macromolecules | Physical Chemistry of Materials | Synthesis of Materials | Nanotechnology | Macromolecular and materials chemistry | Materials Engineering | Nanomaterials | Pharmaceutical sciences | Characterisation of biological macromolecules | Pharmaceutical delivery technologies | Physiology | Characterisation Of Macromolecules | Polymers | Pharmaceutical Sciences | Nanomanufacturing | Receptors and Membrane Biology | Biological Physics | Animal Physiology - Cell | Pharmacology and pharmaceutical sciences | Animal Neurobiology | Macromolecular Chemistry Not Elsewhere Classified | Pharmaceutical Sciences And Pharmacy | Polymers and Plastics | Electrochemical energy storage and conversion | Macromolecular materials | Physical properties of materials | Medicinal and Biomolecular Chemistry | Medical Devices | Structure and dynamics of materials | Biomolecular Modelling and Design | Molecular Medicine | Sensor (Chemical And Bio-) Technology | Anaesthesiology | Nanoscale Characterisation | Medical molecular engineering of nucleic acids and proteins | Macromolecular and Materials Chemistry not elsewhere classified | Health Economics
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in Technology | Expanding Knowledge in the Chemical Sciences | Chemical sciences | Cancer and Related Disorders | Diagnostic Methods | Expanding Knowledge in the Biological Sciences | Inherited Diseases (incl. Gene Therapy) | Human Diagnostics | Education and Training not elsewhere classified | Health not elsewhere classified | Treatments (e.g. chemicals, antibiotics) | Plastic products (incl. Construction materials) | Plastics in primary forms | Nervous system and disorders | Diagnostic methods | Industrial chemicals and related products | Human Pharmaceutical Treatments (e.g. Antibiotics) | Plastics in Primary Forms | Expanding Knowledge in the Physical Sciences | Medical Instruments | Expanding Knowledge in the Information and Computing Sciences | Human Pharmaceutical Products not elsewhere classified |
Related Links
Publications
In situ formation of crosslinked core–corona polymeric nanoparticles from a novel hyperbranched core
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2PY20247F
Bridging Bio-Nano Science and Cancer Nanomedicine
Publisher: American Chemical Society (ACS)
Date: 19-09-2017
Abstract: The interface of bio-nano science and cancer medicine is an area experiencing much progress but also beset with controversy. Core concepts of the field-e.g., the enhanced permeability and retention (EPR) effect, tumor targeting and accumulation, and even the purpose of "nano" in cancer medicine-are hotly debated. In parallel, considerable advances in neighboring fields are occurring rapidly, including the recent progress of "immuno-oncology" and the fundamental impact it is having on our understanding and the clinical treatment of the group of diseases collectively known as cancer. Herein, we (i) revisit how cancer is commonly treated in the clinic and how this relates to nanomedicine (ii) examine the ongoing debate on the relevance of the EPR effect and tumor targeting (iii) highlight ways to improve the next-generation of nanomedicines and (iv) discuss the emerging concept of working with (and not against) biology. While discussing these controversies, challenges, emerging concepts, and opportunities, we explore new directions for the field of cancer nanomedicine.
Multimodal Polymer Nanoparticles with Combined 19F Magnetic Resonance and Optical Detection for Tunable, Targeted, Multimodal Imaging in Vivo
Publisher: American Chemical Society (ACS)
Date: 29-01-2014
DOI: 10.1021/JA410351H
Abstract: Understanding the complex nature of diseased tissue in vivo requires development of more advanced nanomedicines, where synthesis of multifunctional polymers combines imaging multimodality with a biocompatible, tunable, and functional nanomaterial carrier. Here we describe the development of polymeric nanoparticles for multimodal imaging of disease states in vivo. The nanoparticle design utilizes the abundant functionality and tunable physicochemical properties of synthetically robust polymeric systems to facilitate targeted imaging of tumors in mice. For the first time, high-resolution (19)F/(1)H magnetic resonance imaging is combined with sensitive and versatile fluorescence imaging in a polymeric material for in vivo detection of tumors. We highlight how control over the chemistry during synthesis allows manipulation of nanoparticle size and function and can lead to very high targeting efficiency to B16 melanoma cells, both in vitro and in vivo. Importantly, the combination of imaging modalities within a polymeric nanoparticle provides information on the tumor mass across various size scales in vivo, from millimeters down to tens of micrometers.
Switchable 19F MRI polymer theranostics: Towards: in situ quantifiable drug release
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7PY00345E
Abstract: A switchable polymeric 19 F magnetic resonance imaging (MRI) contrast agent was synthesised whereby the transverse ( T 2 ) relaxation times increased as a therapeutic was released from a hyperbranched polymer (HBP) scaffold.
RAFT-functional ionic liquids: towards understanding controlled free radical polymerization in ionic liquids
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B817181P
Bispecific Antibody-Functionalized Upconversion Nanoprobe
Publisher: American Chemical Society (ACS)
Date: 14-02-2018
DOI: 10.1021/ACS.ANALCHEM.7B05341
Abstract: Upconversion nanoparticles (UCNPs) are new optical probes for biological applications. For specific biomolecular recognition to be realized for diagnosis and imaging, the key lies in developing a stable and easy-to-use bioconjugation method for antibody modification. Current methods are not yet satisfactory regarding conjugation time, stability, and binding efficiency. Here, we report a facile and high-yield approach based on a bispecific antibody (BsAb) free of chemical reaction steps. One end of the BsAb is designed to recognize methoxy polyethylene glycol-coated UCNPs, and the other end of the BsAb is designed to recognize the cancer antigen biomarker. Through simple vortexing, BsAb-UCNP nanoprobes form within 30 min and show higher (up to 54%) association to the target than that of the traditional UCNP nanoprobes in the ELISA-like assay. We further demonstrate its successful binding to the cancer cells with high efficiency and specificity for background-free fluorescence imaging under near-infrared excitation. This method suggests a general approach broadly suitable for functionalizing a range of nanoparticles to specifically target biomolecules.
Confinement of Therapeutic Enzymes in Selectively Permeable Polymer Vesicles by Polymerization-Induced Self-Assembly (PISA) Reduces Antibody Binding and Proteolytic Susceptibility
Publisher: American Chemical Society (ACS)
Date: 16-05-2018
Innovative Therapeutic Strategies for Effective Treatment of Brain Metastases
Publisher: MDPI AG
Date: 14-03-2019
DOI: 10.3390/IJMS20061280
Abstract: Brain metastases are the most prevalent of intracranial malignancies. They are associated with a very poor prognosis and near 100% mortality. This has been the case for decades, largely because we lack effective therapeutics to augment surgery and radiotherapy. Notwithstanding improvements in the precision and efficacy of these life-prolonging treatments, with no reliable options for adjunct systemic therapy, brain recurrences are virtually inevitable. The factors limiting intracranial efficacy of existing agents are both physiological and molecular in nature. For ex le, heterogeneous permeability, abnormal perfusion and high interstitial pressure oppose the conventional convective delivery of circulating drugs, thus new delivery strategies are needed to achieve uniform drug uptake at therapeutic concentrations. Brain metastases are also highly adapted to their microenvironment, with complex cross-talk between the tumor, the stroma and the neural compartments driving speciation and drug resistance. New strategies must account for resistance mechanisms that are frequently engaged in this milieu, such as HER3 and other receptor tyrosine kinases that become induced and activated in the brain microenvironment. Here, we discuss molecular and physiological factors that contribute to the recalcitrance of these tumors, and review emerging therapeutic strategies, including agents targeting the PI3K axis, immunotherapies, nanomedicines and MRI-guided focused ultrasound for externally controlling drug delivery.
Influence of charge on hemocompatibility and immunoreactivity of polymeric nanoparticles
Publisher: American Chemical Society (ACS)
Date: 05-09-2018
Controlled Dispersion Polymerization of Methyl Methacrylate in Supercritical Carbon Dioxide via RAFT
Publisher: American Chemical Society (ACS)
Date: 25-01-2008
DOI: 10.1021/MA702017R
‘Isothermal’ phase transitions and supramolecular architecture changes in thermoresponsive polymers via acid-labile side-chains
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C0PY00080A
Antibody-Based Formats to Target Glioblastoma: Overcoming Barriers to Protein Drug Delivery
Publisher: American Chemical Society (ACS)
Date: 19-04-2022
DOI: 10.1021/ACS.MOLPHARMACEUT.1C00996
Abstract: Glioblastoma (GB) is recognized as the most aggressive form of primary brain cancer. Despite advances in treatment strategies that include surgery, radiation, and chemotherapy, the median survival time (∼15 months) of patients with GB has not significantly improved. The poor prognosis of GB is also associated with a very high chance of tumor recurrence (∼90%), and current treatment measures have failed to address the complications associated with this disease. However, targeted therapies enabled through antibody engineering have shown promise in countering GB when used in combination with conventional approaches. Here, we discuss the challenges in conventional as well as future GB therapeutics and highlight some of the known advantages of using targeted biologics to overcome these impediments. We also review a broad range of potential alternative routes that could be used clinically to administer anti-GB biologics to the brain through evasion of its natural barriers.
Confined microemulsion sono-polymerization of poly(ethylene glycol) nanoparticles for targeted delivery
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2CC01874H
Abstract: Confined sono-polymerization is developed to prepare poly(ethylene glycol) nanoparticles within water-in-oil microemulsions for targeted delivery.
Engineering Fluorescent Gold Nanoclusters Using Xanthate-Functionalized Hydrophilic Polymers: Toward Enhanced Monodispersity and Stability
Publisher: American Chemical Society (ACS)
Date: 22-12-2020
Controlling the Biological Fate of Micellar Nanoparticles: Balancing Stealth and Targeting
Publisher: American Chemical Society (ACS)
Date: 16-09-2020
One-Step Chemoenzymatic Synthesis of Poly(ε-caprolactone-block-methyl methacrylate) in Supercritical CO2
Publisher: American Chemical Society (ACS)
Date: 04-07-2006
DOI: 10.1021/MA060046Y
Effects of Surface Charge of Hyperbranched Polymers on Cytotoxicity, Dynamic Cellular Uptake and Localization, Hemotoxicity, and Pharmacokinetics in Mice
Publisher: American Chemical Society (ACS)
Date: 08-11-2017
DOI: 10.1021/ACS.MOLPHARMACEUT.7B00611
Abstract: Nanoscaled polymeric materials are increasingly being investigated as pharmaceutical products, drug/gene delivery vectors, or health-monitoring devices. Surface charge is one of the dominant parameters that regulates nanomaterial behavior in vivo. In this paper, we demonstrated how control over chemical synthesis allowed manipulation of nanoparticle surface charge, which in turn greatly influenced the in vivo behavior. Three methacrylate/methacrylamide-based monomers were used to synthesize well-defined hyperbranched polymers (HBP) by reversible addition-fragmentation chain transfer (RAFT) polymerization. Each HBP had a hydrodynamic diameter of approximately 5 nm as determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Incorporation of a fluorescent moiety within the polymeric nanoparticles allowed determination of how charge affected the in vivo pharmacokinetic behavior of the nanomaterials and the biological response to them. A direct correlation between surface charge, cellular uptake, and cytotoxicity was observed, with cationic HBPs exhibiting higher cellular uptake and cytotoxicity than their neutral and anionic counterparts. Evaluation of the distribution of the differently charged HBPs within macrophages showed that all HBPs accumulated in the cytoplasm, but cationic HBPs also trafficked to, and accumulated within, the nucleus. Although cationic HBPs caused slight hemolysis, this was generally below accepted levels for in vivo safety. Analysis of pharmacokinetic behavior showed that cationic and anionic HBPs had short blood half-lives of 1.82 ± 0.51 and 2.34 ± 0.93 h respectively, compared with 5.99 ± 2.30 h for neutral HBPs. This was attributed to the fact that positively charged surfaces are more readily covered with opsonin proteins and thus more visible to phagocytic cells. This was supported by in vitro flow cytometric and qualitative live cell imaging studies, which showed that cationic HBPs tended to be taken up by macrophages more effectively and rapidly than neutral and anionic particles.
Hyperbranched polymers for molecular imaging: designing polymers for parahydrogen induced polarisation (PHIP)
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C1CC16077J
Abstract: The first hyperpolarisation of polymers using parahydrogen induced polarisation (PHIP) is reported by hydrogenation of terminal alkyne groups in a biocompatible hyperbranched polymer. Signal enhancements of 1500-fold could be obtained depending on the structure of the polymer, thus opening new potential avenues for polymeric molecular imaging.
Functional Hyperbranched Polymers: Toward Targeted in Vivo 19F Magnetic Resonance Imaging Using Designed Macromolecules
Publisher: American Chemical Society (ACS)
Date: 26-03-2010
DOI: 10.1021/JA100252Y
Abstract: We have demonstrated the design and synthesis of hyperbranched molecules that can be successfully imaged in vivo using (19)F MRI in under 10 min. These polymers are cytocompatible following chain extension with PEGMA. In addition, functionalization of these macromolecules can be achieved in a facile manner and with accessible and correct ligand presentation. Such hyperbranched polymers hold promise as new generation tracking and targeting MRI contrast agents.
Modified Organosilica Core-Shell Nanoparticles for Stable pH Sensing in Biological Solutions
Publisher: American Chemical Society (ACS)
Date: 10-04-2018
DOI: 10.1021/ACSSENSORS.8B00034
Abstract: Continuous monitoring using nanoparticle-based sensors has been successfully employed in complex biological systems, yet the sensors still suffer from poor long-term stability partially because of the scaffold materials chosen to date. Organosilica core-shell nanoparticles containing a mixture of covalently incorporated pH-sensitive (shell) and pH-insensitive (core) fluorophores is presented as a continuous pH sensor for application in biological media. In contrast to previous studies focusing on similar materials, we sought to investigate the sensor characteristics (dynamic range, sensitivity, response time, stability) as a function of material properties. The ratio of the fluorescence intensities at specific wavelengths was found to be highly sensitive to pH over a physiologically relevant range (4.5-8) with a response time of <100 ms, significantly faster than that of previously reported response times using silica-based particles. Particles produced stable, pH-specific signals when stored at room temperature for more than 80 days. Finally, we demonstrated that the nanosensors successfully monitored the pH of a bacterial culture over 15 h and that pH changes in the skin of mouse cadavers could also be observed via in vivo fluorescence imaging following subcutaneous injection. The understanding gained from linking sensor characteristics and material properties will inform the next generation of optical nanosensors for continuous-monitoring applications.
Person-Specific Biomolecular Coronas Modulate Nanoparticle Interactions with Immune Cells in Human Blood
Publisher: American Chemical Society (ACS)
Date: 28-10-2020
A Method for Controlling the Aggregation of Gold Nanoparticles: Tuning of Optical and Spectroscopic Properties
Publisher: American Chemical Society (ACS)
Date: 21-06-2013
DOI: 10.1021/LA401361U
Abstract: Gold nanoparticles (AuNPs) have many interesting optical properties, which are derived from their surface plasmon resonance (SPR). However, the SPR of single AuNPs occurs around 520 nm, which is a limitation for biomedical imaging applications, because the maximum falls outside the tissue transparency window (∼650-1000 nm). Here the aggregation of AuNPs is mediated by balancing aggregation and steric stabilization processes. This is achieved by varying the relative amounts of hydrophobic small molecules, which act as aggregating agents, and end functional hydrophilic polymers that serve as steric stabilizing agents. This approach allows the position of the SPR shifted into the tissue transparency window, while maintaining colloidal stability. Importantly, increased depolarized scattering and surface enhanced Raman scattering (SERS) cross sections in this region are achieved compared to the single nanoparticles. By varying the structure of the aggregating agent slightly, the SERS spectra exhibit significant changes, thus demonstrating the potential to encode different aggregates. The aggregates have potential applications in biomedical imaging, as an encoding strategy for combinatorial chemistry, and for use in flow cytometry applications.
Investigation of a Dual siRNA/Chemotherapy Delivery System for Breast Cancer Therapy
Publisher: American Chemical Society (ACS)
Date: 10-05-2022
“Living” Polymer Beads in Supercritical CO2
Publisher: American Chemical Society (ACS)
Date: 04-04-2007
DOI: 10.1021/MA062724M
Enhanced delivery of siRNA to triple negative breast cancer cells in vitro and in vivo through functionalizing lipid-coated calcium phosphate nanoparticles with dual target ligands
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7NR08644J
Abstract: An optimized dual-target lipid-coated calcium phosphate-based nanoplatform efficiently delivers the drug/gene to triple-negative human breast tumor cells in vitro and in vivo .
One-Pot Synthesis of Block Copolymers in Supercritical Carbon Dioxide: A Simple Versatile Route to Nanostructured Microparticles
Publisher: American Chemical Society (ACS)
Date: 28-02-2012
DOI: 10.1021/JA210577H
Abstract: We present a one-pot synthesis for well-defined nanostructured polymeric microparticles formed from block copolymers that could easily be adapted to commercial scale. We have utilized reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare block copolymers in a dispersion polymerization in supercritical carbon dioxide, an efficient process which uses no additional solvents and hence is environmentally acceptable. We demonstrate that a wide range of monomer types, including methacrylates, acrylamides, and styrenics, can be utilized leading to block copolymer materials that are hiphilic (e.g., poly(methyl methacrylate)-b-poly(N,N-dimethylacrylamide)) and/or mechanically erse (e.g., poly(methyl methacrylate)-b-poly(N,N-dimethylaminoethylmethacrylate)). Interrogation of the internal structure of the microparticles reveals an array of nanoscale morphologies, including multilayered, curved cylindrical, and spherical domains. Surprisingly, control can also be exerted by changing the chemical nature of the constituent blocks and it is clear that selective CO(2) sorption must strongly influence the block copolymer phase behavior, resulting in kinetically trapped morphologies that are different from those conventionally observed for block copolymer thin films formed in absence of CO(2).
Polysiloxanes polymers with hyperbranched structure and multivinyl functionality
Publisher: Wiley
Date: 16-11-2011
DOI: 10.1002/POLA.25072
Next-Generation Polymeric Nanomedicines for Oncology: Perspectives and Future Directions
Publisher: Wiley
Date: 07-08-2020
Temperature Dependence of the Dielectric Properties of 2,2′-Azobis(2-methyl-butyronitrile) (AMBN)
Publisher: American Chemical Society (ACS)
Date: 23-02-2010
DOI: 10.1021/IE901389A
Template-Assisted Antibody Assembly: A Versatile Approach for Engineering Functional Antibody Nanoparticles
Publisher: American Chemical Society (ACS)
Date: 07-04-2022
Self-Assembled Hyperbranched Polymer–Gold Nanoparticle Hybrids: Understanding the Effect of Polymer Coverage on Assembly Size and SERS Performance
Publisher: American Chemical Society (ACS)
Date: 02-01-2013
DOI: 10.1021/LA304034B
Abstract: In the past few years, remarkable progress has been made in unveiling novel and unique optical properties of strongly coupled plasmonic nanostructures. However, the application of such plasmonic nanostructures in biomedicine remains challenging because of the lack of facile and robust assembly methods for producing stable nanostructures. Previous attempts to achieve plasmonic nanoassemblies using molecular ligands were limited by the lack of flexibility that could be exercised in forming them. Here, we report the utilization of tailor-made hyperbranched polymers (HBP) as linkers to assemble gold nanoparticles (NPs) into nanoassemblies. The ease and flexibility in tuning the particle size and number of branch ends of an HBP make it an ideal candidate as a linker, as opposed to DNA, small organic molecules, and linear or dendrimeric polymers. We report a strong correlation of polymer (HBP) concentration with the size of the hybrid nanoassemblies and "hot-spot" density. We have shown that such solutions of stable HBP-gold nanoassemblies can be barcoded with various Raman tags to provide improved surface-enhanced Raman scattering (SERS) compared to that of nonaggregated NP systems. These Raman-barcoded hybrid nanoassemblies, with further optimization of the NP shape, size, and hot-spot density, may find application as diagnostic tools in nanomedicine.
Nanobody-displaying porous silicon nanoparticles for the co-delivery of siRNA and doxorubicin
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0BM01335H
Abstract: Targeted delivery of chemotherapeutics to cancer cells has the potential to yield high drug concentrations in cancer cells while minimizing any unwanted side effects.
Successful dispersion polymerization in supercritical CO2 using polyvinylalkylate hydrocarbon surfactants synthesized and anchored via RAFT
Publisher: American Chemical Society (ACS)
Date: 21-08-2008
DOI: 10.1021/JA8046156
Abstract: New CO2-philic hydrocarbon molecules were synthesized by reversible addition fragmentation chain-transfer polymerization. These poly(vinyl alkylates) show the highest solubility in supercritical CO2 of any hydrocarbon reported to date. By utilizing the anchoring ability of the thiocarbonylthio end group, the dispersion polymerization of N-vinyl pyrrolidone was successfully achieved in scCO2 leading to high yields of well-defined spherical polymer particles.
Delivery of PEGylated liposomal doxorubicin by bispecific antibodies improves treatment in models of high-risk childhood leukemia
Publisher: American Association for the Advancement of Science (AAAS)
Date: 17-05-2023
DOI: 10.1126/SCITRANSLMED.ABM1262
Abstract: High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells. Here, we report on the generation of bispecific antibodies (BsAbs) with dual binding to a leukemic cell receptor, such as CD19, CD20, CD22, or CD38, and methoxy polyethylene glycol (PEG) for the targeted delivery of PEGylated liposomal drugs to leukemia cells. This liposome targeting system follows a “mix-and-match” principle where BsAbs were selected on the specific receptors expressed on leukemia cells. BsAbs improved the targeting and cytotoxic activity of a clinically approved and low-toxic PEGylated liposomal formulation of doxorubicin (Caelyx) toward leukemia cell lines and patient-derived s les that are immunophenotypically heterogeneous and representative of high-risk subtypes of childhood leukemia. BsAb-assisted improvements in leukemia cell targeting and cytotoxic potency of Caelyx correlated with receptor expression and were minimally detrimental in vitro and in vivo toward expansion and functionality of normal peripheral blood mononuclear cells and hematopoietic progenitors. Targeted delivery of Caelyx using BsAbs further enhanced leukemia suppression while reducing drug accumulation in the heart and kidneys and extended overall survival in patient-derived xenograft models of high-risk childhood leukemia. Our methodology using BsAbs therefore represents an attractive targeting platform to potentiate the therapeutic efficacy and safety of liposomal drugs for improved treatment of high-risk leukemia.
Recent Advances in the Generation of Antibody–Nanomaterial Conjugates
Publisher: Wiley
Date: 29-09-2018
Abstract: Targeted nanomedicines have significantly changed the way new therapeutics are designed to treat disease. Central to successful therapeutics is the ability to control the dynamics of protein-nanomaterial interactions to enhance the therapeutic effect of the nanomedicine. The aim of this review is to illustrate the ersity and versatility of the conjugation approaches involved in the synthesis of antibody-nanoparticle conjugates, and highlight significant new advances in the field of bioconjugation. Such nanomedicines have found utility as both advanced therapeutic agents, as well as more complex imaging contrast agents that can provide both anatomical and functional information of diseased tissue. While such conjugates show significant promise as next generation targeted nanomedicines, it is recognized that there are in fact no clinically approved targeted therapeutics on the market. This fact is reflected upon within this review, and attempts are made to draw some reasoning from the complexities associated with the bioconjugation chemistry approaches that are typically utilized. Present trends, as well as future directions of next generation targeted nanomedicines are also discussed.
Probing the Biocompatibility and Immune Cell Association of Chiral, Water-Soluble, Bottlebrush Poly(2-oxazoline)s
Publisher: American Chemical Society (ACS)
Date: 05-12-2022
Biodegradable Core−Shell Materials via RAFT and ROP: Characterization and Comparison of Hyperbranched and Microgel Particles
Publisher: American Chemical Society (ACS)
Date: 10-02-2011
DOI: 10.1021/MA1027092
Enhanced drug delivery to cancer cells through a pH-sensitive polycarbonate platform
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2BM01626E
Abstract: In this paper we a report a pH-sensitive polycarbonate conjugated with the anticancer drug c tothecin that shows enhanced drug delivery towards cancer cells.
HRP-mediated inverse emulsion polymerisation of acrylamide in supercritical carbon dioxide
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B804080J
Controlled polymerisation of lactide using an organo-catalyst in supercritical carbon dioxide
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1GC15344G
Cyanine-5-Driven Behaviours of Hyperbranched Polymers Designed for Therapeutic Delivery Are Cell-Type Specific and Correlated with Polar Lipid Distribution in Membranes
Publisher: MDPI AG
Date: 02-07-2021
DOI: 10.3390/NANO11071745
Abstract: The ability to predict the behaviour of polymeric nanomedicines can often be obfuscated by subtle modifications to the corona structure, such as incorporation of fluorophores or other entities. However, these interactions provide an intriguing insight into how selection of molecular components in multifunctional nanomedicines contributes to the overall biological fate of such materials. Here, we detail the internalisation behaviours of polymeric nanomedicines across a suite of cell types and extrapolate data for distinguishing the underlying mechanics of cyanine-5-driven interactions as they pertain to uptake and endosomal escape. By correlating the variance of rate kinetics with endosomal escape efficiency and endogenous lipid polarity, we identify that observed cell-type dependencies correspond with an underlying susceptibility to dye-mediated effects and nanomedicine accumulation within polar vesicles. Further, our results infer that the ability to translocate endosomal membranes may be improved in certain cell types, suggesting a potential role for diagnostic moieties in trafficking of drug-loaded nanocarriers.
Non-Viral Vector-Mediated Gene Therapy for ALS: Challenges and Future Perspectives.
Publisher: American Chemical Society (ACS)
Date: 19-05-2021
DOI: 10.1021/ACS.MOLPHARMACEUT.1C00297
Abstract: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, for which no effective treatment is yet available to either slow or terminate it. Recent advances in gene therapy renew hope for developing an effective approach to control this disease. Non-viral vectors, such as lipid- and polymer-based nanoparticles, cationic polymers, and exosomes, can effectively transfer genes into primary neurons. The resulting gene expression can be long-term, stable, and without immunological complications, which is essential for the effective management of neurological disorders. This Review will first describe the current research and clinical stage of novel therapies for ALS. It will then touch on the journey of non-viral vector use in ALS, subsequently highlighting the application of non-viral vector-mediated gene therapy. The bottlenecks in the translation of non-viral vectors for ALS treatment are also discussed, including the biological barriers of systemic administration and the issues of "when, where, and how much?" for effective gene delivery. The prospect of employing emerging techniques, such as CRISPR-Cas9 gene editing, stem cell methodology, and low-intensity focused ultrasound for fueling the transport of non-viral vectors to the central nervous system for personalized gene therapy, is briefly discussed in the context of ALS. Despite the challenging road that lies ahead, with the current expansion in interest and technological advancement in non-viral vector-delivered gene therapy for ALS, we hold hope that the field is headed toward a positive future.
High-pressure real-time 129Xe NMR: monitoring of surfactant conformation during the self-assembly of reverse micelles in supercritical carbon dioxide
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/B927029A
Abstract: High-pressure (129)Xe NMR has been used to monitor in real time the self-assembly of reverse water-in-supercritical carbon dioxide micelles in the absence of shear, without the need for sensitivity enhancement techniques such as hyperpolarization.
Utilizing PET and MALDI Imaging for Discovery of a Targeted Probe for Brain Endocannabinoid α/β-Hydrolase Domain 6 (ABHD6)
Publisher: American Chemical Society (ACS)
Date: 14-12-2022
Reversible Addition Fragmentation Chain Transfer (
RAFT
) Polymerization: Mechanism, Process and Applications
Publisher: Wiley
Date: 13-01-2012
DOI: 10.1002/9781119953678.RAD058
Abstract: The present article gives an overview of the reversible addition fragmentation chain transfer (RAFT) process. RAFT is one of the most versatile living radical polymerization systems and yields polymers of predictable chain length and narrow molecular weight distribution. RAFT relies on the rapid exchange of thiocarbonyl thio groups between growing polymeric chains. The key strengths of the RAFT process for polymer design are its high tolerance of monomer functionality and reaction conditions, the wide range of well‐controlled polymeric architectures achievable, and its (in‐principle) non‐rate‐retarding nature. This article introduces the mechanism of polymerization, the range of polymer molecular weights achievable, the range of monomers in which polymerization is controlled by RAFT, the various polymeric architectures that can be obtained, the type of end‐group functionalities available to RAFT‐made polymers, and the process of RAFT polymerization.
NMR as a probe of nanostructured domains in ionic liquids: Does domain segregation explain increased performance of free radical polymerisation?
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1SC00207D
Development and Validation of a Targeted Treatment for Brain Tumors Using a Multi-Drug Loaded, Relapse-Resistant Polymeric Theranostic
Publisher: American Chemical Society (ACS)
Date: 05-05-2023
SERS‐based detection of barcoded gold nanoparticle assemblies from within animal tissue
Publisher: Wiley
Date: 15-10-2013
DOI: 10.1002/JRS.4399
Effect of solvent quality on the solution properties of assemblies of partially fluorinated amphiphilic diblock copolymers
Publisher: American Chemical Society (ACS)
Date: 17-10-2012
DOI: 10.1021/MA3019188
Synthesis of Graft Copolymers by the Combination of ATRP and Enzymatic ROP in scCO2
Publisher: American Chemical Society (ACS)
Date: 12-2006
DOI: 10.1021/MA061068N
Surface polymer imprinted optical fibre sensor for dose detection of dabrafenib
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0AN00434K
Abstract: Dabrafenib is one of the most widely used of the new generation of targeted anti-cancer drugs.
New Structure Formation on γ-irradiation of Poly(chlorotrifluoroethylene)
Publisher: Elsevier BV
Date: 08-2003
Understanding the Uptake of Nanomedicines at Different Stages of Brain Cancer Using a Modular Nanocarrier Platform and Precision Bispecific Antibodies
Publisher: American Chemical Society (ACS)
Date: 28-04-2020
Synthesis, characterisation and evaluation of hyperbranched N-(2-hydroxypropyl) methacrylamides for transport and delivery in pancreatic cell lines in vitro and in vivo
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1BM01548F
Abstract: Hyperbranched polyHPMA materials penetrate deep into pancreatic cancer spheroids and a hyperbranched polymer-gemcitabine conjugate showed potency in vitro and in vivo .
Supramolecular Fluorine Magnetic Resonance Spectroscopy Probe Polymer Based on Passerini Bifunctional Monomer
Publisher: American Chemical Society (ACS)
Date: 15-10-2019
Novel one pot synthesis of silver nanoparticle–polymer composites by supercritical CO2 polymerisation in the presence of a RAFT agent
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B710503G
Abstract: We report the one pot synthesis of a silver-polymer nanocomposite in supercritical carbon dioxide (scCO(2)) whereby an organometallic silver complex is thermally decomposed in the presence of a reversible addition fragmentation chain transfer (RAFT) agent during a polymerisation reaction in which the RAFT agent simultaneously stabilises the growing polymer microparticles and the formation of surface located silver nanoparticles.
Synthesis and Phase Behavior of CO2-Soluble Hydrocarbon Copolymer: Poly(vinyl acetate-alt-dibutyl maleate)
Publisher: American Chemical Society (ACS)
Date: 04-02-2010
DOI: 10.1021/MA902505H
Hyperbranched polymers as delivery vectors for oligonucleotides
Publisher: Wiley
Date: 05-04-2012
DOI: 10.1002/POLA.26055
Synthesis of biscarboxylic acid functionalised EDTA mimicking polymers and their ability to form Zr(iv ) chelation mediated nanostructures
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0PY00304B
Abstract: We present a new biscarboxylic acid acrylate, which is used for the synthesis of double hydrophilic EDTA-mimicking block copolymers capable of self-assembly upon zirconium complexation.
New vinyl ester copolymers as stabilisers for dispersion polymerisation in scCO2
Publisher: Elsevier BV
Date: 11-2011
Modulating Targeting of Poly(ethylene glycol) Particles to Tumor Cells Using Bispecific Antibodies
Publisher: Wiley
Date: 14-03-2019
Abstract: Low-fouling or "stealth" particles composed of poly(ethylene glycol) (PEG) display a striking ability to evade phagocytic cell uptake. However, functionalizing them for specific targeting is challenging. To address this challenge, stealth PEG particles prepared by a mesoporous silica templating method are functionalized with bispecific antibodies (BsAbs) to obtain PEG-BsAb particles via a one-step binding strategy for cell and tumor targeting. The dual specificity of the BsAbs-one arm binds to the PEG particles while the other targets a cell antigen (epidermal growth factor receptor, EGFR)-is exploited to modulate the number of targeting ligands per particle. Increasing the BsAb incubation concentration increases the amount of BsAb tethered to the PEG particles and enhances targeting and internalization into breast cancer cells overexpressing EGFR. The degree of BsAb functionalization does not significantly reduce the stealth properties of the PEG particles ex vivo, as assessed by their interactions with primary human blood granulocytes and monocytes. Although increasing the BsAb amount on PEG particles does not lead to the expected improvement in tumor accumulation in vivo, BsAb functionalization facilitates tumor cell uptake of PEG particles. This work highlights strategies to balance evading nonspecific clearance pathways, while improving tumor targeting and accumulation.
Polymer design and component selection contribute to uptake, distribution & trafficking behaviours of polyethylene glycol hyperbranched polymers in live MDA-MB-468 breast cancer cells
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9BM00957D
Abstract: Properties of hyperbranched polymer surface chemistry control cellular distribution.
Biocatalytic Polymerization in Exotic Solvents
Publisher: Wiley
Date: 24-11-2010
Pre-targeting of polymeric nanomaterials to balance tumour accumulation and clearance.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2CC02443H
Abstract: Pre-targeting of bispecific antibodies is probed to enhance tumour retention while limiting clearance of administered multifunctional branched PEGylated nanomedicines. The temporal influence of pre-targeting on polymer interaction with tumour cells and tissue is explored using
Click‐on Antibody Fragments for Customisable Targeted Nanomedicines – Site‐specific Tetrazine and Azide Functionalisation through Non‐canonical Amino Acid incorporation
Publisher: Wiley
Date: 23-10-2023
Gold Nanocluster-Mediated Cellular Death under Electromagnetic Radiation.
Publisher: American Chemical Society (ACS)
Date: 15-11-2017
Abstract: Gold nanoclusters (Au NCs) have become a promising nanomaterial for cancer therapy because of their biocompatibility and fluorescent properties. In this study, the effect of ultrasmall protein-stabilized 2 nm Au NCs on six types of mammalian cells (fibroblasts, B-lymphocytes, glioblastoma, neuroblastoma, and two types of prostate cancer cells) under electromagnetic radiation is investigated. Cellular association of Au NCs in vitro is concentration-dependent, and Au NCs have low intrinsic toxicity. However, when Au NC-incubated cells are exposed to a 1 GHz electromagnetic field (microwave radiation), cell viability significantly decreases, thus demonstrating that Au NCs exhibit specific microwave-dependent cytotoxicity, likely resulting from localized heating. Upon i.v. injection in mice, Au NCs are still present at 24 h post administration. Considering the specific microwave-dependent cytotoxicity and low intrinsic toxicity, our work suggests the potential of Au NCs as effective and safe nanomedicines for cancer therapy.
One-Step Chemoenzymatic Synthesis of Poly(ε-caprolactone-block-methyl methacrylate) in Supercritical CO2. Volume 39, Number 16, August 8, 2006, pp 5352−5358.
Publisher: American Chemical Society (ACS)
Date: 21-02-2007
DOI: 10.1021/MA070151N
GECO-DOSY Post-Processing Analysis of Polymers
Publisher: American Chemical Society (ACS)
Date: 27-01-2007
DOI: 10.1021/MA061345Q
Dependence of Block Copolymer Domain Spacing and Morphology on the Cation Structure of Ionic Liquid Additives
Publisher: American Chemical Society (ACS)
Date: 31-10-2018
Modular Construction of Multifunctional Bioresponsive Cell-Targeted Nanoparticles for Gene Delivery
Publisher: American Chemical Society (ACS)
Date: 11-01-2011
DOI: 10.1021/BC100149G
Abstract: Multifunctional and modular block copolymers prepared from biocompatible monomers and linked by a bioreducible disulfide linkage have been prepared using a combination of ring-opening and atom-transfer radical polymerizations (ATRP). The presence of terminal functionality via ATRP allowed cell-targeting folic acid groups to be attached in a controllable manner, while the block copolymer architecture enabled well-defined nanoparticles to be prepared by a water-oil-water double emulsion procedure to encapsulate DNA with high efficiency. Gene delivery assays in a Calu-3 cell line indicated specific folate-receptor-mediated uptake of the nanoparticles, and triggered release of the DNA payload via cleavage of the disulfide link resulted in enhanced transgene expression compared to nonbioreducible analogues. These materials offer a promising and generic means to deliver a wide variety of therapeutic payloads to cells in a selective and tunable way.
Dispersion polymerisation in supercritical CO2 using macro-RAFT agents
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B812827H
Abstract: Fluorinated macro-RAFT agents can act as in situ stabilisers while exhibiting good control over block copolymers formed by dispersion polymerisation in supercritical CO2 to yield well-defined spherical particles with a fluorinated "halo".
Understanding nanomedicine treatment in an aggressive spontaneous brain cancer model at the stage of early blood brain barrier disruption
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.BIOMATERIALS.2022.121416
Abstract: Personalised nanomedicine is an advancing field which has developed significant improvements for targeting therapeutics to aggressive cancer and with fewer side effects. The treatment of gliomas such as glioblastoma (or other brain tumours), with nanomedicine is complicated by a commonly poor accumulation of drugs in tumour tissue owing to the partially intact blood-brain barrier (BBB). Nonetheless, the BBB becomes compromised following surgical intervention, and gradually with disease progression. Increased vasculature permeability generated by a tumour, combined with decreased BBB integrity, offers a mechanism to enhance therapeutic outcomes. We monitored a spontaneous glioma tumour model in immunocompetent mice with ongoing T2-weighted and contrast-enhanced T1-weighted magnetic resonance imaging gradient echo and spin echo sequences to predict an optimal "leakiness" stage for nanomedicine injections. To ascertain the effectiveness of targeted nanomedicines in treating brain tumours, subsequent systemic administration of targeted hyperbranched polymers was then utislised, to deliver the therapeutic payload when both the tumour and brain vascularity had become sufficiently susceptible to allow drug accumulation. Treatment with either doxorubicin-loaded hyperbranched polymer, or the same nanomedicine targeted to an ephrin receptor (EphA2) using a bispecific antibody, resulted in uptake of chemotherapeutic doxorubicin in the tumour and in reduced tumour growth. Compared to vehicle and doxorubicin only, nanoparticle delivered doxorubicin resulted in increased tumour apoptosis, while averting cardiotoxicity. This suggests that polyethylene based (PEGylated)-nanoparticle delivered doxorubicin could provide a more efficient treatment in tumours with a disrupted BBB, and that treatment should commence immediately following detection of gadolinium permeability, with early detection and ongoing 'leakiness' monitoring in susceptible patients being a key factor.
Influence of oxidation upon the CO2 capture performance of a phenolic-resin-derived carbon
Publisher: Elsevier BV
Date: 06-2013
Simultaneous enzymatic ring opening polymerisation and RAFT-mediated polymerisation in supercritical CO2
Publisher: Royal Society of Chemistry (RSC)
Date: 2006
DOI: 10.1039/B611626D
Abstract: This report presents the first simultaneous, metal-free synthesis of block copolymers through combination of enzymatic ring-opening polymerisation of epsilon-caprolactone with RAFT-mediated controlled radical polymerisation of styrene.
Hyperbranched Polymer–Gold Nanoparticle Assemblies: Role of Polymer Architecture in Hybrid Assembly Formation and SERS Activity
Publisher: American Chemical Society (ACS)
Date: 18-02-2014
DOI: 10.1021/LA4047462
Abstract: Plasmonic gold nanoassemblies that self-assemble with the aid of linking molecules or polymers have the potential to yield controlled hierarchies of morphologies and consequently result in materials with tailored optical (e.g., localized surface plasmon resonances (LSPR)) and spectroscopic properties (e.g., surface-enhanced Raman scattering (SERS)). Molecular linkers that are structurally well-defined are promising for forming hybrid nanoassemblies which are stable in aqueous solution and are increasingly finding application in nanomedicine. Despite much ongoing research in this field, the precise role of molecular linkers in governing the morphology and properties of the hybrid nanoassemblies remains unclear. Previously we have demonstrated that branched linkers, such as hyperbranched polymers, with specific anchoring end groups can be successfully employed to form assemblies of gold NPs demonstrating near-infrared SPRs and intense SERS scattering. We herein introduce a tailored polymer as a versatile molecular linker, capable of manipulating nanoassembly morphologies and hot-spot density. In addition, this report explores the role of the polymeric linker architecture, specifically the degree of branching of the tailored polymer in determining the formation, morphology, and properties of the hybrid nanoassemblies. The degree of branching of the linker polymer, in addition to the concentration and number of anchoring groups, is observed to strongly influence the self-assembly process. The assembly morphology shifts primarily from 1D-like chains to 2D plates and finally to 3D-like globular structures, with increase in degree of branching of the macromolecular linker. Insights have been gained into how the morphology influences the SERS performance of these nanoassemblies with respect to hot-spot density. These findings supplement the understanding of the morphology determining nanoassembly formation and pave the way for the possible application of these nanoassemblies as SERS biosensors for medical diagnostics.
Direct Comparison of Poly(ethylene glycol) and Phosphorylcholine Drug-Loaded Nanoparticles In Vitro and In Vivo
Publisher: American Chemical Society (ACS)
Date: 28-04-2020
Stepwise Like Supramolecular Polymerization of Plasmonic Nanoparticle Building Blocks through Complementary Interactions
Publisher: American Chemical Society (ACS)
Date: 18-08-2020
Supercritical CO2: an effective medium for the chemo-enzymatic synthesis of block copolymers?
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B701128H
Abstract: In this review, we describe the combination of enzymatic polymerisation and controlled free radical polymerisation in supercritical carbon dioxide. This combination facilitates the preparation of a range of block and graft copolymers, some of which cannot easily be obtained by conventional polymer synthesis. Biocatalysis in polymer science provides significant new opportunities and will open up a very broad range of new polymeric materials.
Effect of supercritical carbon dioxide on the loading and release of model drugs from polyurethane films: Comparison with solvent casting
Publisher: Wiley
Date: 02-12-2014
Modulating Macrophage Clearance of Nanoparticles: Comparison of Small-Molecule and Biologic Drugs as Pharmacokinetic Modifiers of Soft Nanomaterials
Publisher: American Chemical Society (ACS)
Date: 07-09-2022
DOI: 10.1021/ACS.MOLPHARMACEUT.2C00528
Abstract: Nanomedicines show benefits in overcoming the limitations of conventional drug delivery systems by reducing side effects, toxicity, and exhibiting enhanced pharmacokinetic (PK) profiles to improve the therapeutic window of small-molecule drugs. However, upon administration, many nanoparticles (NPs) prompt induction of host innate immune responses, which in combination with other clearance pathways such as renal and hepatic, eliminate up to 99% of the administered dose. Here, we explore a drug predosing strategy to transiently suppress the mononuclear phagocyte system (MPS), subsequently improving the PK profile and biological behaviors exhibited by a model NP system [hyperbranched polymers (HBPs)] in an immunocompetent mouse model.
Polymers as Probes for Multimodal Imaging with MRI
Publisher: Wiley
Date: 22-10-2012
Stability of Trithiocarbonate RAFT Agents Containing Both a Cyano and a Carboxylic Acid Functional Group
Publisher: American Chemical Society (ACS)
Date: 07-03-2017
Enhanced uptake of nanoparticle drug carriers via a thermoresponsive shell enhances cytotoxicity in a cancer cell line
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2BM00184E
In Vivo Fate of Carbon Nanotubes with Different Physicochemical Properties for Gene Delivery Applications
Publisher: American Chemical Society (ACS)
Date: 27-03-2017
Abstract: Gene therapy has arisen as a pioneering technique to treat diseases by direct employment of nucleic acids as medicine. The major historical problem is to develop efficient and safe systems for the delivery of therapeutic genes into the target cells. Carbon nanotubes (CNTs) have demonstrated considerable promise as delivery vectors due to their (i) high aspect ratio and (ii) capacity to translocate through plasma membranes, known as the nanoneedle effect. To leverage these advantages, close attention needs to be paid to the physicochemical characteristics of the CNTs used. CNTs with different diameters (thinner and thicker) were treated by chemical oxidation to produce shorter fragments. Rigid (thick) and flexible (thin) CNTs, and their shortened versions, were coated with polyallylamine (ppAA) by plasma-enhanced chemical vapor deposition. The ppAA coating leads to a positively charged CNT surface that is able to electrostatically bind the green fluorescent protein plasmid reporter. This study shows how rigidity and length can affect their (i) behavior in biological media, (ii) ability to transfect in vitro, and (iii) biodistribution in vivo. This study also generates a set of basic design rules for the development of more efficient CNT-based gene-delivery vectors.
Simultaneous Dynamic Kinetic Resolution in Combination with Enzymatic Ring-Opening Polymerization
Publisher: American Chemical Society (ACS)
Date: 20-09-2006
DOI: 10.1021/MA0614388
Charge Has a Marked Influence on Hyperbranched Polymer Nanoparticle Association in Whole Human Blood
Publisher: American Chemical Society (ACS)
Date: 17-05-2017
Fluorophore Selection and Incorporation Contribute to Permeation and Distribution Behaviors of Hyperbranched Polymers in Multi-Cellular Tumor Spheroids and Xenograft Tumor Models.
Publisher: American Chemical Society (ACS)
Date: 25-02-2021
Abstract: Improving our understanding of how design choices in materials synthesis impact biological outcomes is of critical importance in the development of nanomedicines. Here, we show that fluorophore labeling of polymer nanomedicine candidates significantly alters their transport and cell association in multi-cellular tumor spheroids and their penetration in breast cancer xenografts, dependent on the type of the fluorophore and their positioning within the macromolecular structure. These data show the critical importance of the biomaterials structure and architecture in their tissue distribution and intracellular trafficking, which in turn govern their potential therapeutic efficacy. The broader implication of these findings suggests that when developing materials for medical applications, great care should be taken early on in the design process as relatively simple choices may have downstream impacts that could potentially skew preclinical biology data.
Dielectric Properties of Free-Radical Polymerizations: Molecularly Symmetrical Initiators during Thermal Decomposition
Publisher: American Chemical Society (ACS)
Date: 08-01-2010
DOI: 10.1021/IE901201H
RAFT Polymer–Antibody Conjugation: Squaramide Ester Chemistry Leads to Conjugates with a Therapeutic Anti-EGFR Antibody with Full Retention of Activity and Increased Tumor Uptake In Vivo
Publisher: American Chemical Society (ACS)
Date: 23-05-2023
Targeted and modular architectural polymers employing bioorthogonal chemistry for quantitative therapeutic delivery
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0SC00078G
Abstract: There remain several key challenges to existing therapeutic systems for cancer therapy, such as quantitatively determining the true, tissue-specific drug release profile in vivo , as well as reducing side-effects for an increased standard of care.
Development of targeted micelles and polymersomes prepared from degradable RAFT-based diblock copolymers and their potential role as nanocarriers for chemotherapeutics
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2PY00257D
Abstract: Modern polymerisation techniques allow synthesis of functional block copolymers that can self-assemble into degradable nanoparticles (NPs) of different sizes and conformations.
Molecular imaging with polymers
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2PY20132A
Epoxy functionalised poly(ε-caprolactone): synthesis and application
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B810297J
Abstract: Glycidol is used as an initiator for ring-opening polymerisation of epsilon-caprolactone (epsilon-CL) to synthesise epoxy-functionalised poly(epsilon-caprolactone) (PCL) in a reaction catalysed by lipase, and the epoxy-functionalised PCL was further copolymerised with carbon dioxide or anhydride to produce novel graft or hyperbranched copolymers.
Structure-Property Relationships of Organic Electrolytes and Their Effects on Li/S Battery Performance.
Publisher: Wiley
Date: 16-06-2017
Abstract: Electrolytes, which are a key component in electrochemical devices, transport ions between the sulfur/carbon composite cathode and the lithium anode in lithium-sulfur batteries (LSBs). The performance of a LSB mostly depends on the electrolyte due to the dissolution of polysulfides into the electrolyte, along with the formation of a solid-electrolyte interphase. The selection of the electrolyte and its functionality during charging and discharging is intricate and involves multiple reactions and processes. The selection of the proper electrolyte, including solvents and salts, for LSBs strongly depends on its physical and chemical properties, which is heavily controlled by its molecular structure. In this review, the fundamental properties of organic electrolytes for LSBs are presented, and an attempt is made to determine the relationship between the molecular structure and the properties of common organic electrolytes, along with their effects on the LSB performance.
Controlled Dispersion Polymerization in Supercritical Carbon Dioxide
Publisher: CSIRO Publishing
Date: 2009
DOI: 10.1071/CH09081
Abstract: Recent advances in controlled polymerization have led to increased activity in controlled free radical polymerization in unconventional solvents. This short report focuses on the renewed interest in dispersion polymerization in supercritical CO2 brought about by the application of controlled free radical polymerization techniques. The emergence of novel and industrially-applicable materials is discussed, as well as the dependence of material properties and morphology upon factors such as surfactant type and how it is employed during the polymerization.
Equilibrium Swelling Measurements of Network and Semicrystalline Polymers in Supercritical Carbon Dioxide Using High-Pressure NMR
Publisher: American Chemical Society (ACS)
Date: 30-03-2005
DOI: 10.1021/MA0503108
Importance of Polymer Length in Fructose-Based Polymeric Micelles for an Enhanced Biological Activity
Publisher: American Chemical Society (ACS)
Date: 10-01-2019
Self-cyclisation as a general and efficient platform for peptide and protein macrocyclisation
Publisher: Cold Spring Harbor Laboratory
Date: 13-07-2022
DOI: 10.1101/2022.07.12.499226
Abstract: Macrocyclisation of proteins and peptides results in a remarkable increase in structural stability, making cyclic peptides and proteins of great interest in drug discovery—either directly as drug leads or as in the case of cyclised nanodiscs (cNDs), as tools for studies of trans-membrane receptors and membrane-active peptides. Various biological methods have been developed that are capable of yielding head-to-tail macrocyclised products. Such enzymatic methods require careful optimisation of cyclisation over polymerisation. Here, we describe the engineering of self-cyclising “ autocyclase ” proteins, where an intramolecular rearrangement can be triggered to yield a monomeric cyclic product in high yields. We characterise the self-cyclisation reaction mechanism and demonstrate how the unimolecular reaction path can circumvent existing challenges of enzymatic cyclisation. We use the method to produce several notable cyclic peptides and proteins, demonstrating how autocyclases offer a simple and scalable way to access a vast ersity of macrocyclic biomolecules.
The influence of domain segregation in ionic liquids upon controlled polymerisation mechanisms: RAFT polymerisation
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2PY20835K
A study of the radiation chemistry of poly(chlorotrifluoroethylene) by ESR spectroscopy
Publisher: Elsevier BV
Date: 12-2003
Biodegradable core crosslinked star polymer nanoparticles as 19F MRI contrast agents for selective imaging
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3PY01311A
Responsive hybrid block co-polymer conjugates of proteins–controlled architecture to modulate substrate specificity and solution behaviour
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1PY00128K
Nanoparticle based medicines: approaches for evading and manipulating the mononuclear phagocyte system and potential for clinical translation
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2BM00181K
Abstract: Nanomedicine recognition and clearance by the mononuclear phagocyte system (MPS) impedes optimal clinical impacts for this class of materials. We present an overview of factors involved in MPS interactions and approaches to overcome this barrier.
NMR Microscopy: A Tool for Measuring Monomer Diffusion in Supercritical CO2
Publisher: Wiley
Date: 29-08-2006
Preparation of Sodium-Capped Poly(lactic acid) Oligomers by Catalytic Initiation with a Sodium α-, β-, or γ-Hydroxyacids
Publisher: American Chemical Society (ACS)
Date: 24-11-2009
DOI: 10.1021/MA901861U
Pharmacokinetics and Biodistribution of 89Zr-Miltuximab and Its Antibody Fragments as Glypican-1 Targeting Immuno-PET Agents in Glioblastoma
Publisher: American Chemical Society (ACS)
Date: 05-01-2023
Aptamer-targeted hyperbranched polymers: towards greater specificity for tumours in vivo
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3CC00127J
Abstract: Hyperbranched polymers conjugated to a peptide-aptamer were prepared using a combination of RAFT polymerisation and click chemistry for targeting tumour cells in vivo. The polymers showed enhanced cell-uptake in vitro (compared to unconjugated polymer) while excellent specificity for solid tumours was observed in vivo using a mouse model of melanoma.
Oral Delivery of Multicompartment Nanomedicines for Colorectal Cancer Therapeutics: Combining Loco‐Regional Delivery with Cell‐Target Specificity
Publisher: Wiley
Date: 11-12-2020
Celebrating Women in the Pharmaceutical Sciences
Publisher: American Chemical Society (ACS)
Date: 08-03-2021
Designed multifunctional polymeric nanomedicines: long-term biodistribution and tumour accumulation of aptamer-targeted nanomaterials
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8CC05831H
Abstract: We report a novel multifunctional hyperbranched polymer based on polyethylene glycol (PEG) as a nanomedicine platform that facilitates longitudinal and quantitative 89 Zr-PET imaging, enhancing knowledge of nanomaterial biodistribution and pharmacokinetics harmacodynamics both in vivo and ex vivo .
Effect of Molecular Architecture on the Performance of 19 F NMR Imaging Agents
Publisher: American Chemical Society
Date: 2011
The impact of polymer size and cleavability on the intravenous pharmacokinetics of PEG-based hyperbranched polymers in rats
Publisher: MDPI AG
Date: 08-12-2020
DOI: 10.3390/NANO10122452
Abstract: A better understanding of the impact of molecular size and linkers is important for PEG-based hyperbranched polymers (HBPs) intended as tailored drug delivery vehicles. This study aimed to evaluate the effects of crosslinker chemistry (cleavable disulphide versus non-cleavable ethylene glycol methacrylate (EGDMA) linkers) and molecular weight within the expected size range for efficient renal elimination (22 vs. 48 kDa) on the intravenous pharmacokinetic and biodistribution properties of 89Zr-labelled HBPs in rats. All HBPs showed similar plasma pharmacokinetics over 72 h, despite differences in linker chemistry and size. A larger proportion of HBP with the cleavable linker was eliminated via the urine and faeces compared to a similar-sized HBP with the non-cleavable linker, while size had no impact on the proportion of the dose excreted. The higher molecular weight HBPs accumulated in organs of the mononuclear phagocyte system (liver and spleen) more avidly than the smaller HBP. These results suggest that HBPs within the 22 to 48 kDa size range show no differences in plasma pharmacokinetics, but distinct patterns of organ biodistribution and elimination are evident.
One-pot controlled synthesis of biodegradable and biocompatible co-polymer micelles
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B821736J
Investigation of spontaneous microemulsion formation in supercritical carbon dioxide using high-pressure NMR
Publisher: Elsevier BV
Date: 08-2006
Exploring the impact of severity in hepatic fibrosis disease on the intrahepatic distribution of novel biodegradable nanoparticles targeted towards different disease biomarkers
Publisher: Elsevier BV
Date: 11-2023
Kinetics of Enzymatic Ring-Opening Polymerization of ε-Caprolactone in Supercritical Carbon Dioxide
Publisher: American Chemical Society (ACS)
Date: 20-10-2006
DOI: 10.1021/MA061310Q
Investigation of the Therapeutic Potential of a Synergistic Delivery System through Dual Controlled Release of Camptothecin–Doxorubicin
Publisher: Wiley
Date: 21-02-2020
Using Peptide Aptamer Targeted Polymers as a Model Nanomedicine for Investigating Drug Distribution in Cancer Nanotheranostics
Publisher: American Chemical Society (ACS)
Date: 07-09-2017
DOI: 10.1021/ACS.MOLPHARMACEUT.7B00560
Abstract: Theranostics is a strategy that combines multiple functions such as targeting, stimulus-responsive drug release, and diagnostic imaging into a single platform, often with the aim of developing personalized medicine.1,2 Based on this concept, several well-established hyperbranched polymeric theranostic nanoparticles were synthesized and characterized as model nanomedicines to investigate how their properties affect the distribution of loaded drugs at both the cell and whole animal levels. An 8-mer peptide aptamer was covalently bound to the periphery of the nanoparticles to achieve both targeting and potential chemosensitization functionality against heat shock protein 70 (Hsp70). Doxorubicin was also bound to the polymeric carrier as a model chemotherapeutic drug through a degradable hydrazone bond, enabling pH-controlled release under the mildly acid conditions that are found in the intracellular compartments of tumor cells. In order to track the nanoparticles, cyanine-5 (Cy5) was incorporated into the polymer as an optical imaging agent. In vitro cellular uptake was assessed for the hyperbranched polymer containing both doxorubicin (DOX) and Hsp70 targeted peptide aptamer in live MDA-MB-468 cells, and was found to be greater than that of either the untargeted, DOX-loaded polymer or polymer alone due to the specific affinity of the peptide aptamer for the breast cancer cells. This was also validated in vivo with the targeted polymers showing much higher accumulation within the tumor 48 h postinjection than the untargeted analogue. More detailed assessment of the nanomedicine distribution was achieved by directly following the polymeric carrier and the doxorubicin at both the in vitro cellular level via compartmental analysis of confocal images of live cells and in whole tumors ex vivo using confocal imaging to visualize the distribution of the drug in tumor tissue as a function of distance from blood vessels. Our results indicate that this polymeric carrier shows promise as a cancer theranostic, demonstrating active targeting to tumor cells with the capability for simultaneous drug release.
Combination of Chemotherapy and Mild Hyperthermia Using Targeted Nanoparticles: A Potential Treatment Modality for Breast Cancer
Publisher: MDPI AG
Date: 30-04-2023
DOI: 10.3390/PHARMACEUTICS15051389
Abstract: Despite the clinical benefits that chemotherapeutics has had on the treatment of breast cancer, drug resistance remains one of the main obstacles to curative cancer therapy. Nanomedicines allow therapeutics to be more targeted and effective, resulting in enhanced treatment success, reduced side effects, and the possibility of minimising drug resistance by the co-delivery of therapeutic agents. Porous silicon nanoparticles (pSiNPs) have been established as efficient vectors for drug delivery. Their high surface area makes them an ideal carrier for the administration of multiple therapeutics, providing the means to apply multiple attacks to the tumour. Moreover, immobilising targeting ligands on the pSiNP surface helps direct them selectively to cancer cells, thereby reducing harm to normal tissues. Here, we engineered breast cancer-targeted pSiNPs co-loaded with an anticancer drug and gold nanoclusters (AuNCs). AuNCs have the capacity to induce hyperthermia when exposed to a radiofrequency field. Using monolayer and 3D cell cultures, we demonstrate that the cell-killing efficacy of combined hyperthermia and chemotherapy via targeted pSiNPs is 1.5-fold higher than applying monotherapy and 3.5-fold higher compared to using a nontargeted system with combined therapeutics. The results not only demonstrate targeted pSiNPs as a successful nanocarrier for combination therapy but also confirm it as a versatile platform with the potential to be used for personalised medicine.
Cellular Targeting of Bispecific Antibody-Functionalized Poly(ethylene glycol) Capsules: Do Shape and Size Matter?
Publisher: American Chemical Society (ACS)
Date: 08-2019
Abstract: In the present study, a capsule system that consists of a stealth carrier based on poly(ethylene glycol) (PEG) and functionalized with bispecific antibodies (BsAbs) is introduced to examine the influence of the capsule shape and size on cellular targeting. Hollow spherical and rod-shaped PEG capsules with tunable aspect ratios (ARs) of 1, 7, and 18 were synthesized and subsequently functionalized with BsAbs that exhibit dual specificities to PEG and epidermal growth factor receptor (EGFR). Dosimetry (variation between the concentrations of capsules present and capsules that reach the cell surface) was controlled through "dynamic" incubation (i.e., continuously mixing the incubation medium). The results obtained were compared with those obtained from the "static" incubation experiments. Regardless of the incubation method and the capsule shape and size studied, BsAb-functionalized PEG capsules showed >90% specific cellular association to EGFR-positive human breast cancer cells MDA-MB-468 and negligible association with both control cell lines (EGFR negative Chinese hamster ovary cells CHO-K1 and murine macrophages RAW 264.7) after incubation for 5 h. When dosimetry was controlled and the dose concentration was normalized to the capsule surface area, the size or shape had a minimal influence on the cell association behavior of the capsules. However, different cellular internalization behaviors were observed, and the capsules with ARs 7 and 18 were, respectively, the least and most optimal shape for achieving high cell internalization under both dynamic and static conditions. Dynamic incubation showed a greater impact on the internalization of rod-shaped capsules (∼58-67% change) than on the spherical capsules (∼24-29% change). The BsAb-functionalized PEG capsules reported provide a versatile particle platform for the evaluation and comparison of cellular targeting performance of capsules with different sizes and shapes in vitro.
Hyperbranched Poly(2-oxazoline)s and Poly(ethylene glycol): A Structure–Activity Comparison of Biodistribution
Publisher: American Chemical Society (ACS)
Date: 20-07-2020
Protected amine-functional initiators for the synthesis of α-amine homo- and heterotelechelic poly(2-ethyl-2-oxazoline)s
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2PY00649A
Abstract: Screening a series of protected amine cationic ring-opening polymerization initiators revealed the commercially available N -(3-bromopropyl)phthalimide as the most suitable to achieve defined polymers with high degree of amine functionalization.
pH-responsive star polymer nanoparticles: potential 19F MRI contrast agents for tumour-selective imaging
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3PY00654A
Related Organisations
University Of Nottingham
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
Linkage Projects - Grant ID: LP0990817
Start Date: 08-2010
End Date: 03-2015
Amount: $300,000.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP1094205
Start Date: 2010
End Date: 12-2012
Amount: $265,000.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP0880032
Start Date: 10-2008
End Date: 04-2012
Amount: $285,000.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE170100206
Start Date: 05-2017
End Date: 12-2017
Amount: $550,000.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP140100951
Start Date: 2014
End Date: 02-2017
Amount: $370,000.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE160100168
Start Date: 2016
End Date: 03-2017
Amount: $650,000.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP220103135
Start Date: 09-2022
End Date: 08-2025
Amount: $510,000.00
Funder: Australian Research Council
View Funded ActivityIndustrial Transformation Training Centres - Grant ID: IC170100035
Start Date: 12-2017
End Date: 06-2024
Amount: $4,743,710.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE110100033
Start Date: 05-2011
End Date: 12-2013
Amount: $150,000.00
Funder: Australian Research Council
View Funded ActivityARC Future Fellowships - Grant ID: FT110100284
Start Date: 2012
End Date: 12-2015
Amount: $667,267.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE230100048
Start Date: 03-2023
End Date: 03-2024
Amount: $570,702.00
Funder: Australian Research Council
View Funded ActivityLinkage Projects - Grant ID: LP150100703
Start Date: 06-2016
End Date: 06-2019
Amount: $360,000.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE150100067
Start Date: 2015
End Date: 06-2016
Amount: $390,000.00
Funder: Australian Research Council
View Funded ActivityLinkage Projects - Grant ID: LP220100450
Start Date: 2023
End Date: 12-2025
Amount: $492,895.00
Funder: Australian Research Council
View Funded ActivityIndustrial Transformation Research Hubs - Grant ID: IH220100017
Start Date: 09-2023
End Date: 09-2028
Amount: $4,808,669.00
Funder: Australian Research Council
View Funded ActivityARC Centres Of Excellence - Grant ID: CE140100036
Start Date: 06-2014
End Date: 06-2021
Amount: $26,000,000.00
Funder: Australian Research Council
View Funded ActivityLinkage Projects - Grant ID: LP180100486
Start Date: 11-2019
End Date: 12-2022
Amount: $390,000.00
Funder: Australian Research Council
View Funded ActivityLinkage - International - Grant ID: LX0776233
Start Date: 2007
End Date: 05-2010
Amount: $35,000.00
Funder: Australian Research Council
View Funded Activity