ORCID Profile
0000-0001-9900-2644
Current Organisations
ETH Zürich
,
Monash Institute of Pharmaceutical Sciences
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Nanomaterials | Nanotechnology | Nanomedicine | Synthesis of Materials | Nanobiotechnology | Nanofabrication, Growth and Self Assembly
Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Technology |
Publisher: Wiley
Date: 21-07-2021
Abstract: The breadth and the shape of molecular weight distributions can significantly influence fundamental polymer properties that are critical for various applications. However, current approaches require the extensive synthesis of multiple polymers, are limited in dispersity precision and are typically incapable of simultaneously controlling both the dispersity and the shape of molecular weight distributions. Here we report a simplified approach, whereby on mixing two polymers (one of high Đ and one of low Đ ), any intermediate dispersity value can be obtained (e.g. from 1.08 to 1.84). Unrivalled precision is achieved, with dispersity values obtained to even the nearest 0.01 (e.g. 1.37→1.38→1.39→1.40→1.41→1.42→1.43→1.44→1.45), while maintaining fairly monomodal molecular weight distributions. This approach was also employed to control the shape of molecular weight distributions and to obtain diblock copolymers with high dispersity accuracy. The straightforward nature of our methodology alongside its compatibility with a wide range of polymerisation protocols (e.g. ATRP, RAFT), significantly expands the toolbox of tailored polymeric materials and makes them accessible to all researchers.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6PY02158A
Abstract: A facile, high-scale, and versatile technique to prepare biocompatible nanoparticles with tailorable properties from thermoresponsive macro-CTAs and macro-stabilizers.
Publisher: Wiley
Date: 09-10-2023
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1SC04241F
Abstract: The dispersity of polymers is efficiently controlled in aqueous atom transfer radical polymerization by modulating the reversible dissociation of the bromide ion from the copper deactivator.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7CC05842J
Abstract: We report a straightforward approach for preparing polymers with lipidic chain ends, and show their application in stabilising nanostructured drug delivery vehicles.
Publisher: Wiley
Date: 25-06-2020
Publisher: Wiley
Date: 24-10-2017
Abstract: The scope and accessibility of sequence-controlled multiblock copolymers is demonstrated by direct "in situ" polymerization of hydrophobic, hydrophilic and fluorinated monomers. Key to the success of this strategy is the ability to synthesize ABCDE, EDCBA and EDCBABCDE sequences with high monomer conversions (>98 %) through iterative monomer additions, yielding excellent block purity and low overall molar mass dispersities (Ð<1.16). Small-angle X-ray scattering showed that certain sequences can form well-ordered mesostructures. This synthetic approach constitutes a simple and versatile platform for expanding the availability of tailored polymeric materials from readily available monomers.
Publisher: American Chemical Society (ACS)
Date: 29-08-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9PY01435G
Abstract: Sequence-controlled copolymers have recently attracted great interest in a variety of applications, including antimicrobial materials.
Publisher: Elsevier BV
Date: 11-2020
Publisher: American Chemical Society (ACS)
Date: 16-04-2011
DOI: 10.1021/BM200219E
Abstract: We report the synthesis of a low cytotoxic polycation that maintains its cationic strength for well over a few hours then degrades into a benign polymer with nontoxic byproducts. Well-defined poly(2-dimethylaminoethyl acrylate) (PDMAEA) of five different molecular weights prepared using reversible addition-fragmentation chain transfer (RAFT) "living" radical polymerization degrades slowly over 200 h (∼8 days). As this degradation is independent of both the polymer molecular weight and solution pH, it is consistent with a self-catalyzed hydrolysis process without the need for an internal or external degradation trigger. In addition, the polymer shows little or no cytotoxicity to HeLa cells for the molecular weights of 5600 and below, even at very high polymer concentrations (equivalent to a nitrogen hosphorus ratio of 200). Therefore, at sufficiently low molecular weights this polymer has the essential attributes (i.e., ability to autodegradable and low toxicity) for a delivery carrier suitable for DNA or siRNA.
Publisher: MDPI AG
Date: 02-02-2020
Abstract: Poly(ethylene glycol) (PEG) is widely used as a gold standard in bioconjugation and nanomedicine to prolong blood circulation time and improve drug efficacy. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles is a well-established technique known as PEGylation, with PEGylated products have been using in clinics for the last few decades. However, it is increasingly recognized that treating patients with PEGylated drugs can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). Anti-PEG antibodies are also found in patients who have never been treated with PEGylated drugs but have consumed products containing PEG. Consequently, treating patients who have acquired anti-PEG antibodies with PEGylated drugs results in accelerated blood clearance, low drug efficacy, hypersensitivity, and, in some cases, life-threatening side effects. In this succinct review, we collate recent literature to draw the attention of polymer chemists to the issue of PEG immunogenicity in drug delivery and bioconjugation, thereby highlighting the importance of developing alternative polymers to replace PEG. Several promising yet imperfect alternatives to PEG are also discussed. To achieve asatisfactory alternative, further joint efforts of polymer chemists and scientists in related fields are urgently needed to design, synthesize and evaluate new alternatives to PEG.
Publisher: Wiley
Date: 11-01-2022
Abstract: Controlled polymerizations have enabled the production of nanostructured materials with different shapes, each exhibiting distinct properties. Despite the importance of shape, current morphological transformation strategies are limited in polymer scope, alter the chemical structure, require high temperatures, and are fairly tedious. Herein we present a rapid and versatile morphological transformation strategy that operates at room temperature and does not impair the chemical structure of the constituent polymers. By simply adding a molecular transformer to an aqueous dispersion of polymeric nanoparticles, a rapid evolution to the next higher-order morphology was observed, yielding a range of morphologies from a single starting material. Significantly, this approach can be applied to nanoparticles produced by disparate block copolymers obtained by various synthetic techniques including emulsion polymerization, polymerization-induced self-assembly and traditional solution self-assembly.
Publisher: American Chemical Society (ACS)
Date: 29-09-2017
DOI: 10.1021/ACS.BIOMAC.7B00995
Abstract: Polymerization-induced self-assembly (PISA) is a facile one-pot synthetic technique for preparing polymeric nanoparticles with different sizes and shapes for application in a variety of fields including nanomedicine. However, the in vivo biodistribution of nanoparticles obtained by PISA still remains unclear. To address this knowledge gap, we report the synthesis, cytotoxicity, and biodistribution in an in vivo tumor-bearing mouse model of polystyrene micelles with various sizes and polystyrene filomicelles with different lengths prepared by PISA. First, a library of nanoparticles was prepared comprised of poly(glycidyl methacrylate)-b-poly(oligo(ethylene glycol) methyl ether methacrylate)-b-polystyrene polymers, and their size and morphology were tuned by varying the polystyrene block length without affecting the surface chemistry. The
Publisher: Wiley
Date: 25-07-2018
Abstract: The size and surface chemistry of nanoparticles dictate their interactions with biological systems. However, it remains unclear how these key physicochemical properties affect the cellular association of nanoparticles under dynamic flow conditions encountered in human vascular networks. Here, the facile synthesis of novel fluorescent nanoparticles with tunable sizes and surface chemistries and their association with primary human umbilical vein endothelial cells (HUVECs) is reported. First, a one-pot polymerization-induced self-assembly (PISA) methodology is developed to covalently incorporate a commercially available fluorescent dye into the nanoparticle core and tune nanoparticle size and surface chemistry. To characterize cellular association under flow, HUVECs are cultured onto the surface of a synthetic microvascular network embedded in a microfluidic device (SynVivo, INC). Interestingly, increasing the size of carboxylic acid-functionalized nanoparticles leads to higher cellular association under static conditions but lower cellular association under flow conditions, whereas increasing the size of tertiary amine-decorated nanoparticles results in a higher level of cellular association, under both static and flow conditions. These findings provide new insights into the interactions between polymeric nanomaterials and endothelial cells. Altogether, this work establishes innovative methods for the facile synthesis and biological characterization of polymeric nanomaterials for various potential applications.
Publisher: Wiley
Date: 11-08-2023
Abstract: Although controlled radical polymerization is an excellent tool to make precision polymeric materials, reversal of the process to retrieve the starting monomer is far less explored despite the significance of chemical recycling. Here, we investigate the bulk depolymerization of RAFT and ATRP‐synthesized polymers under identical conditions. RAFT‐synthesized polymers undergo a relatively low‐temperature solvent‐free depolymerization back to monomer thanks to the partial in situ transformation of the RAFT end‐group to macromonomer. Instead, ATRP‐synthesized polymers can only depolymerize at significantly higher temperatures ( °C) through random backbone scission. To aid a more complete depolymerization at even lower temperatures, we performed a facile and quantitative end‐group modification strategy in which both ATRP and RAFT end‐groups were successfully converted to macromonomers. The macromonomers triggered a lower temperature bulk depolymerization with an onset at 150 °C yielding up to 90 % of monomer regeneration. The versatility of the methodology was demonstrated by a scalable depolymerization (≈10 g of starting polymer) retrieving 84 % of the starting monomer intact which could be subsequently used for further polymerization. This work presents a new low‐energy approach for depolymerizing controlled radical polymers and creates many future opportunities as high‐yielding, solvent‐free and scalable depolymerization methods are sought.
Publisher: American Chemical Society (ACS)
Date: 13-04-2017
DOI: 10.1021/JACS.7B01694
Abstract: A highly efficient photomediated atom transfer radical polymerization protocol is reported for semi-fluorinated acrylates and methacrylates. Use of the commercially available solvent, 2-trifluoromethyl-2-propanol, optimally balances monomer, polymer, and catalyst solubility while eliminating transesterification as a detrimental side reaction. In the presence of UV irradiation and ppm concentrations of copper(II) bromide and Me
Publisher: American Chemical Society (ACS)
Date: 22-03-2021
Publisher: Wiley
Date: 05-06-2021
DOI: 10.1002/POL.20210319
Abstract: In photo‐atom transfer radical polymerization (ATRP), dispersity can be efficiently controlled by varying the deactivator concentration. In this work, we provide mechanistic insight into dispersity‐controlled photo‐ATRP by conducting detailed kinetics under a range of conditions. For the lower dispersity polymers, a conventional first‐order kinetic profile was observed accompanied by a linear evolution of number average molecular weight ( M n ) with conversion while the reactions reached moderate to high conversions (between 66% and 93%). Whereas, when polymers of high dispersity were targeted, the M n remained relatively constant throughout the polymerization and the reactions ceased at less than 50% of conversion. In particular, for Ð = 1.84, a significant deviation between theoretical and experimental molecular weights was evident. This deviation was unambiguously attributed to slow initiation as indicated by 1 H NMR, where significant percentages of unreacted initiator were observed. Importantly, the addition of ligand at the polymerization plateau re‐initiated the polymerization and led to the complete consumption of the unreacted initiator, thus enabling the synthesis of one‐pot diblock copolymers. We subsequently evaluated the effect of the degree of polymerization (DP) on the obtained dispersity when a constant catalyst ratio was maintained. Based on the interpolation of those experiments results, we could predict experimental conditions for any desirable DPs and dispersities.
Publisher: American Chemical Society (ACS)
Date: 27-07-2015
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2PY20628E
Publisher: American Chemical Society (ACS)
Date: 09-2020
DOI: 10.26434/CHEMRXIV.12895754.V1
Abstract: Controlling monomer sequence in synthetic macromolecules is a major challenge in polymer science and the order of building blocks has already been demonstrated to determine macromolecular folding, self-assembly and fundamental polymer properties. Dispersity is another key parameter in material design, with both low and high dispersity polymers displaying complementary properties and functions. However, synthetic approaches that can simultaneously control both sequence and dispersity remain experimentally unattainable. Here we report a simple, one pot, and rapid synthesis of sequence-controlled multiblocks with on demand control over dispersity while maintaining high livingness, excellent agreement between theoretical and experimental molecular weights and quantitative yields. Key to our approach is the regulation in chain transfer agent activity during controlled radical polymerization that enables the preparation of multiblocks with gradually ascending ( Ɖ =1.16 →1.60), descending ( Ɖ =1.66 →1.22), alternating low and high dispersity values ( Ɖ =1.17 →1.61 →1.24 →1.70 →1.26) or any combination thereof. The enormous potential of our methodology was further demonstrated through the impressive synthesis of highly ordered pentablock, octablock and decablock copolymers yielding the first generation of multiblocks with concurrent control over both sequence and dispersity.
Publisher: American Chemical Society (ACS)
Date: 31-08-2011
DOI: 10.1021/BM2007423
Abstract: The controlled release of siRNA or DNA complexes from cationic polymers is an important parameter design in polymer-based delivery carriers. In this work, we use the self-catalyzed degradable poly(2-dimethylaminoethyl acrylate) (PDMAEA) to strongly bind, protect, and then release oligo DNA (a mimic for siRNA) without the need for a cellular or external trigger. This self-catalyzed hydrolysis process of PDMAEA forms poly(acrylic acid) and N,N'-dimethylamino ethyl ethanol, both of which have little or no toxicity to cells, and offers the advantage of little or no toxicity to off-target cells and tissues. We found that PDMAEA makes an ideal component of a delivery carrier by protecting the oligo DNA for a sufficiently long period of time to transfect most cells (80% transfection after 4 h) and then has the capacity to release the DNA inside the cells after ~10 h. The PDMAEA formed large nanoparticle complexes with oligo DNA of ~400 nm that protected the oligo DNA from DNase in serum. The nanoparticle complexes showed no toxicity for all molecular weights at a nitrogen hosphorus (N/P) ratio of 10. Only the higher molecular weight polymers at very high N/P ratios of 200 showed significant levels of cytotoxicity. These attributes make PDMAEA a promising candidate as a component in the design of a gene delivery carrier without the concern about accumulated toxicity of nanoparticles in the human body after multiadministration, an issue that has become increasingly more important.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2BM00168C
Abstract: Ionizable cationic lipids play a critical role in developing new gene therapies for various biomedical applications, including COVID-19 vaccines. However, it remains unclear whether the formulation of lipid nanoparticles (LNPs) using DLin-MC3-DMA, an optimized ionizable lipid clinically used for small interfering RNA (siRNA) therapy, also facilitates high liver-selective transfection of other gene therapies such as plasmid DNA (pDNA). Here we report the first investigation into pDNA transfection efficiency in different mouse organs after intramuscular and intravenous administration of lipid nanoparticles (LNPs) where DLin-MC3-DMA, DLin-KC2-DMA or DODAP are used as the ionizable cationic lipid component of the LNP. We discovered that these three benchmark lipids previously developed for siRNA delivery followed an unexpected characteristic rank order in gene expression efficiency when utilized for pDNA. In particular, DLin-KC2-DMA facilitated higher
Publisher: American Chemical Society (ACS)
Date: 03-11-2015
Publisher: Elsevier BV
Date: 06-2020
Publisher: American Chemical Society (ACS)
Date: 16-03-2020
Publisher: American Chemical Society (ACS)
Date: 16-01-2013
DOI: 10.1021/BM301721K
Abstract: Triggered-release of encapsulated therapeutics from nanoparticles without remote or environmental triggers was demonstrated in this work. Disassembly of the polymer nanoparticles to unimers at precise times allowed the controlled release of oligo DNA. The polymers used in this study consisted of a hydrophilic block for stabilization and second thermoresponsive block for self-assembly and disassembly. At temperatures below the second block's LCST (i.e., below 37 °C for in vitro assays), the diblock copolymer was fully water-soluble, and when heated to 37 °C, the polymer self-assembled into a narrow size distribution of nanoparticles with an average diameter of approximately 25 nm. The thermoresponsive nature of the second block could be manipulated in situ by the self-catalyzed degradation of cationic 2-(dimethylamino)ethyl acrylate (DMAEA) units to negatively charged acrylic acid groups and when the amount of acid groups was sufficiently high to increase the LCST of the second block above 37 °C. The disassembly of the nanoparticles could be controlled from 10 to 70 h. The use of these nanoparticles as a combined therapy, in which one or more agents can be released in a predetermined way, has the potential to improve the personal point of care treatment of patients.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9SC03546J
Abstract: This review explores the different synthetic methods by which dispersity and MWD shape can be tuned and discusses the different properties and applications where this variation is beneficial.
Publisher: American Chemical Society (ACS)
Date: 15-11-2016
Publisher: American Chemical Society (ACS)
Date: 29-09-2022
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5PY00166H
Abstract: An environmentally friendly emulsion technique produces uniform nanoparticles with precise control over molecular weight and particle size.
Publisher: Wiley
Date: 07-08-2019
Publisher: American Chemical Society (ACS)
Date: 24-08-2023
Publisher: American Chemical Society (ACS)
Date: 31-08-2017
Publisher: Springer Science and Business Media LLC
Date: 18-10-2021
Publisher: Elsevier BV
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 21-05-2013
DOI: 10.1038/NCOMMS2905
Abstract: Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2PY01383E
Abstract: Eosin Y is used as a photocatalyst for the acceleration of the depolymerization of polymethacrylates.
Publisher: Wiley
Date: 20-08-2012
DOI: 10.1002/POLA.26313
Publisher: Springer Science and Business Media LLC
Date: 04-11-2019
Publisher: American Chemical Society (ACS)
Date: 10-01-2023
DOI: 10.1021/JACS.2C11757
Publisher: American Chemical Society (ACS)
Date: 10-2021
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3TB21015D
Publisher: Springer Science and Business Media LLC
Date: 17-10-2017
DOI: 10.1038/NCHEM.2634
Abstract: Translating the precise monomer sequence control achieved in nature over macromolecular structure (for ex le, DNA) to whole synthetic systems has been limited due to the lack of efficient synthetic methodologies. So far, chemists have only been able to synthesize monomer sequence-controlled macromolecules by means of complex, time-consuming and iterative chemical strategies such as solid-state Merrifield-type approaches or molecularly dissolved solution-phase systems. Here, we report a rapid and quantitative synthesis of sequence-controlled multiblock polymers in discrete stable nanoscale compartments via an emulsion polymerization approach in which a vinyl-terminated macromolecule is used as an efficient chain-transfer agent. This approach is environmentally friendly, fully translatable to industry and thus represents a significant advance in the development of complex macromolecule synthesis, where a high level of molecular precision or monomer sequence control confers potential for molecular targeting, recognition and biocatalysis, as well as molecular information storage.
Publisher: MDPI AG
Date: 25-05-2021
DOI: 10.3390/NANO11061391
Abstract: Antimicrobial resistance (AMR) is predicted to soon become one of the most serious threats to human and animal health [...]
Publisher: Springer Science and Business Media LLC
Date: 29-11-2021
DOI: 10.1038/S41557-021-00818-8
Abstract: Controlling monomer sequence and dispersity in synthetic macromolecules is a major goal in polymer science as both parameters determine materials' properties and functions. However, synthetic approaches that can simultaneously control both sequence and dispersity remain experimentally unattainable. Here we report a simple, one pot and rapid synthesis of sequence-controlled multiblocks with on-demand control over dispersity while maintaining a high livingness, and good agreement between theoretical and experimental molecular weights and quantitative yields. Key to our approach is the regulation in the activity of the chain transfer agent during a controlled radical polymerization that enables the preparation of multiblocks with gradually ascending (Ɖ = 1.16 → 1.60), descending (Ɖ = 1.66 → 1.22), alternating low and high dispersity values (Ɖ = 1.17 → 1.61 → 1.24 → 1.70 → 1.26) or any combination thereof. We further demonstrate the potential of our methodology through the synthesis of highly ordered pentablock, octablock and decablock copolymers, which yield multiblocks with concurrent control over both sequence and dispersity.
Publisher: MDPI AG
Date: 09-11-2020
DOI: 10.3390/PHARMACEUTICS12111068
Abstract: Targeted delivery of nucleic acids to lymph nodes is critical for the development of effective vaccines and immunotherapies. However, it remains challenging to achieve selective lymph node delivery. Current gene delivery systems target mainly to the liver and typically exhibit off-target transfection at various tissues. Here we report novel lipid nanoparticles (LNPs) that can deliver plasmid DNA (pDNA) to a draining lymph node, thereby significantly enhancing transfection at this target organ, and substantially reducing gene expression at the intramuscular injection site (muscle). In particular, we discovered that LNPs stabilized by 3% Tween 20, a surfactant with a branched poly(ethylene glycol) (PEG) chain linking to a short lipid tail, achieved highly specific transfection at the lymph node. This was in contrast to conventional LNPs stabilized with a linear PEG chain and two saturated lipid tails (PEG-DSPE) that predominately transfected at the injection site (muscle). Interestingly, replacing Tween 20 with Tween 80, which has a longer unsaturated lipid tail, led to a much lower transfection efficiency. Our work demonstrates the importance of PEGylation in selective organ targeting of nanoparticles, provides new insights into the structure–property relationship of LNPs, and offers a novel, simple, and practical PEGylation technology to prepare the next generation of safe and effective vaccines against viruses or tumours.
Publisher: American Chemical Society (ACS)
Date: 26-09-2013
DOI: 10.1021/BM4007858
Abstract: Timed-released disassembly of nanoparticles without a remote trigger or environmental cues is demonstrated in this work. The reversible addition-fragmentation chain transfer (RAFT) polymerization allowed the fine-tuning of the chemical composition in the diblock copolymers, in which the first block consisted of a hydrophilic monomer (DMA) and the second random block consisted of three different monomers: (a) the thermoresponsive NIPAM, (b) the self-catalyzed hydrolyzable DMAEA, and (c) the hydrophobic BA. These diblock copolymers were solubilized in water below the lower critical solution temperature (LCST) of the thermoresponsive second block, and heated to 37 °C (i.e., >LCST) to form small micelle nanoparticles with a narrow particle size distribution. As DMAEA hydrolyzed to acrylic acid groups, the LCST of the diblock increased, and the time at the start of micelle disassembly (t(start)) corresponded to the point where the LCST was equal to the solution temperature (i.e., 37 °C). The high water content in the PNIPAM core allowed an even degradation of the core over time. The copolymer composition allowed fine control over t(start), as this time was linearly dependent upon the BA units in the second block. These nanoparticles could also be designed to be stable (i.e., not disassemble) over a wide pH range or disassemble below a pH of 7.3. Additionally, the time from the start of disassembly to full unimer formation (t(degrade)) could be controlled by the amount of DMAEA units in the second block. A longer t(degrade) (~5.5 h) was found when the number of DMAEA units was 42 compared to t(degrade) of 1.1 h for 25 units. The nanoparticles designed in this work, through fine control of the polymer chemical composition, have the potential for drug delivery purposes for timed-release of drugs and prodrugs and other wide-ranging applications where timed-release would be beneficial.
Publisher: Wiley
Date: 11-08-2023
Abstract: Although controlled radical polymerization is an excellent tool to make precision polymeric materials, reversal of the process to retrieve the starting monomer is far less explored despite the significance of chemical recycling. Here, we investigate the bulk depolymerization of RAFT and ATRP‐synthesized polymers under identical conditions. RAFT‐synthesized polymers undergo a relatively low‐temperature solvent‐free depolymerization back to monomer thanks to the partial in situ transformation of the RAFT end‐group to macromonomer. Instead, ATRP‐synthesized polymers can only depolymerize at significantly higher temperatures ( °C) through random backbone scission. To aid a more complete depolymerization at even lower temperatures, we performed a facile and quantitative end‐group modification strategy in which both ATRP and RAFT end‐groups were successfully converted to macromonomers. The macromonomers triggered a lower temperature bulk depolymerization with an onset at 150 °C yielding up to 90 % of monomer regeneration. The versatility of the methodology was demonstrated by a scalable depolymerization (≈10 g of starting polymer) retrieving 84 % of the starting monomer intact which could be subsequently used for further polymerization. This work presents a new low‐energy approach for depolymerizing controlled radical polymers and creates many future opportunities as high‐yielding, solvent‐free and scalable depolymerization methods are sought.
Publisher: Wiley
Date: 07-08-2019
Abstract: Dispersity significantly affects the properties of polymers. However, current methods for controlling the polymer dispersity are limited to bimodal molecular weight distributions, adulterated polymer chains, or low end-group fidelity and rely on feeding reagents, flow-based, or multicomponent systems. To overcome these limitations, we report a simple batch system whereby photoinduced atom transfer radical polymerisation is exploited as a convenient and versatile technique to control dispersity of both homopolymers and block copolymers. By varying the concentration of the copper complex, a wide range of monomodal molecular weight distributions can be obtained (Đ=1.05-1.75). In all cases, high end-group fidelity was confirmed by MALDI-ToF-MS and exemplified by efficient block copolymer formation (monomodal, Đ=1.1-1.5). Importantly, our approach utilises ppm levels of copper (as low as 4 ppm), can be tolerant to oxygen and exhibits perfect temporal control, representing a major step forward in tuning polymer dispersity for various applications.
Publisher: Wiley
Date: 10-01-2022
Abstract: Controlled polymerizations have enabled the production of nanostructured materials with different shapes, each exhibiting distinct properties. Despite the importance of shape, current morphological transformation strategies are limited in polymer scope, alter the chemical structure, require high temperatures, and are fairly tedious. Herein we present a rapid and versatile morphological transformation strategy that operates at room temperature and does not impair the chemical structure of the constituent polymers. By simply adding a molecular transformer to an aqueous dispersion of polymeric nanoparticles, a rapid evolution to the next higher‐order morphology was observed, yielding a range of morphologies from a single starting material. Significantly, this approach can be applied to nanoparticles produced by disparate block copolymers obtained by various synthetic techniques including emulsion polymerization, polymerization‐induced self‐assembly and traditional solution self‐assembly.
Publisher: American Chemical Society (ACS)
Date: 04-09-2021
DOI: 10.1021/BM401139E
Abstract: An influenza virus-inspired polymer mimic nanocarrier was used to deliver siRNA for specific and near complete gene knockdown of an osteoscarcom cell line (U-2SO). The polymer was synthesized by single-electron transfer living radical polymerization (SET-LRP) at room temperature to avoid complexities of transfer to monomer or polymer. It was the only LRP method that allowed good block copolymer formation with a narrow molecular weight distribution. At nitrogen to phosphorus (N/P) ratios of equal to or greater than 20 (greater than a polymer concentration of 13.8 μg/mL) with polo-like kinase 1 (PLK1) siRNA gave specific and near complete (>98%) cell death. The polymer further degrades to a benign polymer that showed no toxicity even at polymer concentrations of 200 μg/mL (or N/P ratio of 300), suggesting that our polymer nanocarrier can be used as a very effective siRNA delivery system and in a multiple dose administration. This work demonstrates that with a well-designed delivery device, siRNA can specifically kill cells without the inclusion of an additional clinically used highly toxic cochemotherapeutic agent. Our work also showed that this excellent delivery is sensitive for the study of off-target knockdown of siRNA.
Publisher: MDPI AG
Date: 08-04-2021
Abstract: COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9TB01624D
Abstract: For the first time Cu(0)-RDRP conditions were optimised to allow for the fast and controlled polymerisation of vinyl azlactone with tuneable lipid elements: a versatile platform material for the high-throughput synthesis of antimicrobial materials.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6PY01797E
Abstract: Polymerization-induced self-assembly (PISA) is an easily applied synthetic technique for the preparation of polymer nanoparticles with various shapes and at high concentrations.
Publisher: American Chemical Society (ACS)
Date: 10-01-2018
DOI: 10.1021/ACSMACROLETT.7B00978
Abstract: RAFT emulsion polymerization techniques including polymerization-induced self-assembly (PISA) and temperature-induced morphological transformation (TIMT) are widely used to produce noncrosslinked nano-objects with various morphologies. However, the worm, vesicle and lamellar morphologies produced by these techniques typically cannot tolerate the presence of added surfactants, thus limiting their potential applications. Herein we report the surfactant tolerance of noncrosslinked worms, vesicles, and lamellae prepared by RAFT emulsion polymerizations using poly(di(ethylene glycol) ethyl ether methacrylate-
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6TB02787C
Abstract: A new class of oligomeric cationic polymers with lipophilic tails were developed as antibacterial lipopeptide mimics, and revealed structurally dependent bacterial killing.
Publisher: American Chemical Society (ACS)
Date: 29-03-2019
Publisher: American Chemical Society (ACS)
Date: 05-2023
DOI: 10.1021/JACS.3C00589
Publisher: Wiley
Date: 18-05-2017
Publisher: Wiley
Date: 09-08-2018
Abstract: Rapid developments in the polymerization-induced self-assembly (PISA) technique have paved the way for the environmentally friendly production of nanoparticles with tunable size and shape for a erse range of applications. In this feature article, the biomedical applications of PISA nanoparticles and the substantial progress made in controlling their size and shape are highlighted. In addition to early investigations into drug delivery, applications such as medical imaging, tissue culture, and blood cryopreservation are also described. Various parameters for controlling the morphology of PISA nanoparticles are discussed, including the degree of polymerization of the macro-CTA and core-forming polymers, the concentration of macro-CTA and core-forming monomers, the solid content of the final products, the solution pH, the thermoresponsitivity of the macro-CTA, the macro-CTA end group, and the initiator concentration. Finally, several limitations and challenges for the PISA technique that have been recently addressed, along with those that will require further efforts into the future, will be highlighted.
Publisher: Wiley
Date: 04-12-2018
Publisher: American Chemical Society (ACS)
Date: 12-07-2018
Publisher: American Chemical Society (ACS)
Date: 25-10-2018
DOI: 10.1021/ACS.BIOMAC.8B01317
Abstract: There is growing interest in synthetic polymers which co-opt the structural features of naturally occurring antimicrobial peptides. However, our understanding of how macromolecular architecture affects antibacterial activity remains limited. To address this, we investigated whether varying architectures of a series of block and statistical co-oligomers influenced antibacterial and hemolytic activity. Cu(0)-mediated polymerization was used to synthesize oligomers constituting 2-(Boc-amino)ethyl acrylate units and either diethylene glycol ethyl ether acrylate (DEGEEA) or poly(ethylene glycol) methyl ether acrylate units with varying macromolecular architecture subsequent deprotection produced primary amine functional oligomers. Further guanylation provided an additional series of antimicrobial candidates. Both chemical composition and macromolecular architecture were shown to affect antimicrobial activity. A broad spectrum antibacterial oligomer (containing guanidine moieties and DEGEEA units) was identified that possessed promising activity (MIC = 2 μg mL
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2PY00468B
Abstract: Study of the composition, lenght and chemical structure of surface-active statistical copolymers in low-energy miniemulsions.
Publisher: Wiley
Date: 09-10-2023
Publisher: Wiley
Date: 21-07-2021
Abstract: The breadth and the shape of molecular weight distributions can significantly influence fundamental polymer properties that are critical for various applications. However, current approaches require the extensive synthesis of multiple polymers, are limited in dispersity precision and are typically incapable of simultaneously controlling both the dispersity and the shape of molecular weight distributions. Here we report a simplified approach, whereby on mixing two polymers (one of high Đ and one of low Đ ), any intermediate dispersity value can be obtained (e.g. from 1.08 to 1.84). Unrivalled precision is achieved, with dispersity values obtained to even the nearest 0.01 (e.g. 1.37→1.38→1.39→1.40→1.41→1.42→1.43→1.44→1.45), while maintaining fairly monomodal molecular weight distributions. This approach was also employed to control the shape of molecular weight distributions and to obtain diblock copolymers with high dispersity accuracy. The straightforward nature of our methodology alongside its compatibility with a wide range of polymerisation protocols (e.g. ATRP, RAFT), significantly expands the toolbox of tailored polymeric materials and makes them accessible to all researchers.
Publisher: Informa UK Limited
Date: 20-08-2015
DOI: 10.1517/17425247.2014.950564
Abstract: Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy. This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and overall drug efficacy. By comparing spherical and nonspherical nanoparticles, they establish some general design principles to serve as guidelines for developing the next generation of nanocarriers for drug delivery. Pioneering studies on nanoparticles show that nonspherical shapes show great promise as cancer drug delivery vectors. Filamentous or worm-like micelles together with other rare morphologies such as needles or disks may become the norm for next-generation drug carriers, though at present, traditional spherical micelles remain the dominant shape of nanocarriers described in the literature due to synthesis and testing difficulties. The few reports that do exist describing nonspherical nanoparticles show a number of favorable properties that should encourage more efforts to develop facile and versatile nanoparticle synthesis methodologies with the flexibility to create different shapes, tunable sizes and adaptable surface chemistries. In addition, the authors note that there is a current lack of understanding into the factors governing (and optimizing) the inter-relationships of size, surface characteristics and shapes of many nanoparticles proposed for use in cancer therapy.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1PY01044A
Abstract: Herein we present a simple batch method to control polymer dispersity using a mixture of two ATRP initiators with different reactivities.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6CC00900J
Abstract: Thermoresponsive nanoworms with tuneable cores prepared via aqueous RAFT-mediated emulsion polymerizations and temperature-induced morphological transformation (TIMT) technique.
Publisher: American Chemical Society (ACS)
Date: 12-02-2020
DOI: 10.26434/CHEMRXIV.11836137.V1
Abstract: Dispersity ( Ɖ ) can significantly affect polymer properties and is a key parameter in materials design however, current methods do not allow for the comprehensive control of dispersity. They are limited in monomer scope, may require the use of flow-based systems and/or additional reagents ( e.g. termination agents or co-monomers), and are often accompanied by multimodal molecular weight distributions, low initiator efficiencies or poor end-group fidelity. Herein, we report a straightforward and versatile batch method based on reversible addition-fragmentation chain transfer (RAFT) polymerization which enables good control over Ɖ of a wide range of monomer classes, including acrylates, acrylamides, methacrylates and styrene. In addition, our methodology is compatible with more challenging monomers such as methacrylic acid, vinyl ketone and vinyl acetate. Control over Ɖ is achieved by mixing two RAFT agents with sufficiently different transfer activities in various ratios, affording polymers with monomodal molecular weight distributions over a broad dispersity range ( Ɖ ~ 1.09-2.10). Our findings were further supported by simulations through the use of deterministic kinetic modelling which was fully in line with our experimental data, further confirming the power of our methodology. The robustness of the concept is further demonstrated by the preparation of well-defined block copolymers via chain extension of all polymers regardless of the initial Ɖ .
Publisher: American Chemical Society (ACS)
Date: 26-10-2021
Publisher: American Chemical Society (ACS)
Date: 12-02-2020
DOI: 10.26434/CHEMRXIV.11836137
Abstract: Dispersity ( i Ɖ /i ) can significantly affect polymer properties and is a key parameter in materials design however, current methods do not allow for the comprehensive control of dispersity. They are limited in monomer scope, may require the use of flow-based systems and/or additional reagents ( i e.g. /i termination agents or co-monomers), and are often accompanied by multimodal molecular weight distributions, low initiator efficiencies or poor end-group fidelity. Herein, we report a straightforward and versatile batch method based on reversible addition-fragmentation chain transfer (RAFT) polymerization which enables good control over i Ɖ /i of a wide range of monomer classes, including acrylates, acrylamides, methacrylates and styrene. In addition, our methodology is compatible with more challenging monomers such as methacrylic acid, vinyl ketone and vinyl acetate. Control over i Ɖ /i is achieved by mixing two RAFT agents with sufficiently different transfer activities in various ratios, affording polymers with monomodal molecular weight distributions over a broad dispersity range ( i Ɖ /i ~ 1.09-2.10). Our findings were further supported by simulations through the use of deterministic kinetic modelling which was fully in line with our experimental data, further confirming the power of our methodology. The robustness of the concept is further demonstrated by the preparation of well-defined block copolymers via chain extension of all polymers regardless of the initial i Ɖ /i .
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6PY00639F
Abstract: This review highlights the substantial progress in the syntheses and applications of filomicelles, an emerging nanomaterial with distinct and useful properties.
Publisher: American Chemical Society (ACS)
Date: 25-02-2022
DOI: 10.1021/JACS.2C00963
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5RA24361K
Abstract: We report the antibacterial activity of a novel class of low molecular weight cationic polymers synthesised using Cu(0) mediated polymerisation.
Publisher: Wiley
Date: 06-09-2023
DOI: 10.1002/POL.20230479
Publisher: American Chemical Society (ACS)
Date: 09-2020
DOI: 10.26434/CHEMRXIV.12895754
Abstract: Controlling monomer sequence in synthetic macromolecules is a major challenge in polymer science and the order of building blocks has already been demonstrated to determine macromolecular folding, self-assembly and fundamental polymer properties. Dispersity is another key parameter in material design, with both low and high dispersity polymers displaying complementary properties and functions. However, synthetic approaches that can simultaneously control both sequence and dispersity remain experimentally unattainable. Here we report a simple, one pot, and rapid synthesis of sequence-controlled multiblocks with on demand control over dispersity while maintaining high livingness, excellent agreement between theoretical and experimental molecular weights and quantitative yields. Key to our approach is the regulation in chain transfer agent activity during controlled radical polymerization that enables the preparation of multiblocks with gradually ascending ( i Ɖ /i =1.16 →1.60), descending ( i Ɖ /i =1.66 →1.22), alternating low and high dispersity values ( i Ɖ /i =1.17 →1.61 →1.24 →1.70 →1.26) or any combination thereof. The enormous potential of our methodology was further demonstrated through the impressive synthesis of highly ordered pentablock, octablock and decablock copolymers yielding the first generation of multiblocks with concurrent control over both sequence and dispersity.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2PY01563C
Abstract: In the vast majority of atom transfer radical polymerizations, alkyl bromides or alkyl chlorides are commonly employed as initiators. Herein, alkyl iodides are demonstrated as ATRP initiators.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5PY01467K
Abstract: RAFT-mediated emulsion polymerization of styrene and subsequent morphological transition produces nanoaggregates with tuneable morphologies.
Publisher: Informa UK Limited
Date: 13-04-2018
DOI: 10.1080/17425247.2017.1316262
Abstract: Vascular-targeted drug delivery is a promising approach for the treatment of atherosclerosis, due to the vast involvement of endothelium in the initiation and growth of plaque, a characteristic of atherosclerosis. One of the major challenges in carrier design for targeting cardiovascular diseases (CVD) is that carriers must be able to navigate the circulation system and efficiently marginate to the endothelium in order to interact with the target receptors. This review draws on studies that have focused on the role of particle size, shape, and density (along with flow hemodynamics and hemorheology) on the localization of the particles to activated endothelial cell surfaces and vascular walls under different flow conditions, especially those relevant to atherosclerosis. Generally, the size, shape, and density of a particle affect its adhesion to vascular walls synergistically, and these three factors should be considered simultaneously when designing an optimal carrier for targeting CVD. Available preliminary data should encourage more studies to be conducted to investigate the use of nano-constructs, characterized by a sub-micrometer size, a non-spherical shape, and a high material density to maximize vascular wall margination and minimize capillary entrapment, as carriers for targeting CVD.
Publisher: American Chemical Society (ACS)
Date: 19-03-2015
Publisher: Springer Science and Business Media LLC
Date: 24-11-2020
Publisher: Wiley
Date: 09-03-2021
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0PY00823K
Abstract: Here we report a simple and versatile batch methodology to tailor polymer dispersity utilizing PET-RAFT polymerization.
Publisher: American Chemical Society (ACS)
Date: 10-01-2020
Abstract: Antibiotic resistance has made the treatment of biofilm-related infections challenging. As such, the quest for next-generation antimicrobial technologies must focus on targeted therapies to which pathogenic bacteria cannot develop resistance. Stimuli-responsive therapies represent an alternative technological focus due to their capability of delivering targeted treatment. This study provides a proof-of-concept investigation into the use of magneto-responsive gallium-based liquid metal (LM) droplets as antibacterial materials, which can physically damage, disintegrate, and kill pathogens within a mature biofilm. Once exposed to a low-intensity rotating magnetic field, the LM droplets become physically actuated and transform their shape, developing sharp edges. When placed in contact with a bacterial biofilm, the movement of the particles resulting from the magnetic field, coupled with the presence of nanosharp edges, physically ruptures the bacterial cells and the dense biofilm matrix is broken down. The antibacterial efficacy of the magnetically activated LM particles was assessed against both Gram-positive and Gram-negative bacterial biofilms. After 90 min over 99% of both bacterial species became nonviable, and the destruction of the biofilms was observed. These results will impact the design of next-generation, LM-based biofilm treatments.
Start Date: 01-2018
End Date: 11-2023
Amount: $367,446.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2020
End Date: 11-2023
Amount: $450,000.00
Funder: Australian Research Council
View Funded Activity