Publications 2014

ACNs 2014 Publications

For earlier publications click   2013   2011/2012

 

 

Dual Bioresponsive Mesoporous Silica Nanocarrier as an “AND” Logic Gate for Targeted Drug Delivery Cancer Cells

Xin Chen1, Alexander H. Soeriyadi1, Xun Lu1, Sharon M. Sagnella2, Maria Kavallaris2 and J Justin Gooding1,*

 

Cover image for Vol. 24 Issue 39 
 

Despite the rapid development of drug delivery vehicles that react to a specific biological environment, the complexity of triggering drug release in a particular target area remains an enduring challenge. Here, the engineering of bioresponsive polymer-mesoporous silica nanoparticles (MSNs) with function akin to an AND logic gate is described. Polycaprolactone (esterase degradable) is immobilized into the core of MSNs while polyacrylic acid (PAA), which is pH responsive, covered the outside of the MSNs to create a PAA-PCL-MSNs construct. Fluorescence spectroscopy indicates that the construct releases the payload (doxorubicin, cancer drugs) in the presence of, and only in the presence of, both low pH AND esterase. Confocal microscopy and fluorescence lifetime microscopy (FLIM) demonstrate uptake of the intact construct and subsequent intracellular doxorubicin (DOX) delivery into the nucleus. Further in vitro IC50 studies demonstrate the AND logic gate delivery system results in more than an eightfold efficacy against neuroblastoma (SK-N-BE(2)) cells in comparison with normal fibroblasts (MRC-5). These results demonstrate the utility of MSN-polymer construct to create an AND gate capable of selectively delivering a drug payload.

1.School of Chemistry and Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia; 2.Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre and Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia

Analytical Biochemistry 2014 Aug 26;466C:16-18. doi: 10.1016/j.ab.2014.08.002

Monitoring the progression of loop-mediated isothermal amplification using conductivity.

Zhang X1, Liu W2, Lu X3, Justin Gooding J3, Li Q4, Qu K4.

 

Cover image Analytical Biochemistry 

Loop-mediated isothermal amplification (LAMP) yields a large amount of DNA, as well as magnesium pyrophosphate precipitate, causing a decrease in ionic strength that can be measured with a conductivity meter. There is a clear relationship between the conductivity of the LAMP mixture solution and the duration of biochemical reaction. Moreover, there is also a clear relationship between the change in conductivity and the amount of initial template DNA over the range of 0.08 to 3.2ng. These results demonstrate the feasibility not only for detecting the LAMP product qualitatively but also for real-time monitoring the biochemical reaction progression quantitatively using conductivity measurements.

1Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture, Qingdao 266071, People's Republic of China. Electronic address: zhangxz@ysfri.ac.cn2College of Chemistry and ChemicalEngineering, Ocean University of China, Qingdao 266100, People's Republic of China. 3School of Chemistry and The Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2052, Australia. 4Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture, Qingdao 266071, People's Republic of China.

Journal of Biomedical Nanotechnology  (11, Number 4, April 2015, pp. 730-738(9))

Labeling and Tracking of Human Pancreatic Islets Using Carbon Nanotubes

Syed, Farooq; Riggio, Cristina; Masini, Matilde; Bugliani, Marco; Battaglia, Valentina; Novelli, Michela; Suleiman, Mara; Vittorio, Orazio; Boggi, Ugo; Filipponi, Franco; Marselli, Lorella; Bartolozzi, Carlo; Masiello, Pellegrino; Raffa, Vittoria; Marchetti, Piero

 

Limited tools are available for the non-invasive monitoring of transplanted islets. In this study, we have compared the widely used superparamagnetic iron oxide nanoparticle ferumoxide (Endorem®) and multiwalled carbon nanotubes (MWCNTs) for islet cell labeling and tracking. INS-1E cells and human pancreatic islets isolated from 12 non-diabetic cadaveric organ donors (age: 62 ± 16 yr, BMI: 24.6 ± 3.3 kg/m2) were incubated with 50 μg/ml Endorem® or 15 μg/ml MWCNTs and studied after 7 or 14 days to assess beta cell morphology, ultrastructure, function, cell survival and in-vitro and in-vitro magnetic resonance imaging (MRI). Light and electron (EM) microscopy showed the well-maintained morphology and ultrastructure of both INS-1E and human islets during the incubation. EM also revealed the presence of Endorem® and MWCNTs within the beta but not the alpha cells. The compounds did not affect beta cell function and viability, and in-vitro MRI showed that labeled INS-1E cells and human islets could be imaged. Finally, MWCNT labeled human islets were successfully transplanted into the subcutis of rats localized in the desired site via magnetic field and tracked by MRI. These data suggest that MWCNTs can be an alternative labeling compound to be used with human islets for experimental and transplantation studies.

BOOK CHAPTER: (ISBN: 978-3-662-43603-5Metronomic Chemotheraphy

Metronomic Chemotherapy Regimens Using Microtubule-Targeting Agents: Mechanisms of Action, Preclinical Activity and Future Developments

Eddy Pasquier3 4 Maria Kavallaris3 5 Nicolas Andre4 6 7

Metronomic Chemotherapy

Microtubule-targeting agents (MTAs) are amongst the most successful chemotherapeutic drugs commonly used in the clinic for the treatment of human cancers. Although originally administered at or close to the maximum tolerated dose once every 3 weeks, the discovery of their potent antiangiogenic properties at the end of the 1990s has led to the re-evaluation of treatment protocols. Nowadays, MTAs are often administered at lower doses either weekly or even more frequently following a metronomic schedule, thus leading to increased efficacy and decreased toxicity. In this chapter, we present an overview of the in vitro and in vivo studies that have contributed to the development of MTA-based metronomic chemotherapy protocols and increased our understanding of their mechanisms of action. First, we discuss the complex cellular and molecular mechanisms involved in the antiangiogenic activity of MTAs. We also present their effects on the immune system, which may contribute to the antitumour efficacy of MTA-based metronomic chemotherapy. Then, we review the results obtained with this type of therapeutic approach in preclinical models of human cancer, focusing on the most promising combination treatments. Finally, we oversee the future developments in this field in terms of new MTAs and novel formulations currently in development with the aims to improve efficacy and bioavailability while increasing tumour targeting and specificity.                                       

3Tumour Biology and Targeting Program, Children’s Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, 81 Randwick NSW 2031 Australia 4Metronomics Global Health Initiative, Marseille, France 5Australian Centre for Nanomedicine, University of New South Wales Sydney NSW Australia 6Hematology and Pediatric Oncology Department, La Timone University Hospital of Marseille, Marseille France 7Faculty of Pharmacy, INSERM UMR 911, Centre de Recherche en Oncologic biologique et en Oncopharmacologie, Aix-Marseille University, Marseille France

 

CONFERENCE PROCEEDINGS: AIP Proceedings (1586, 35 (2014); http://dx.doi.org/10.1063/1.4866725 Conference date: 23-25 October 2013. Location Surabaya Indonesia)

Modification of porous silicon rugate filters through thiol-yne photochemistry

Alexander H. Soeriyadi1, Ying Zhu1, Peter Reece2, J Justin Gooding3

  aip

Porous silicon (PSi) has a considerable potential as biosensor platform. In particular, the ability to modify the surface chemistry of porous silicon is of interest. Here we present a generic method to modify the surface of porous silicon through thiol-yne photochemistry initiated by a radical initiator. Firstly, a freshly etched porous silicon substrate is modified through thermal hydrosilylation with 1,8-nonadiyne to passivate the surface and introduce alkyne functionalities. The alkyne functional surface could then be further reacted with thiol species in the presence of a radical initiator and UV light. Functionalization of the PSi rugate filter is followed with optical reflectivity measurements as well as high resolution X-ray photoelectron spectroscopy (XPS).

1Australian Centre for Nanomedicine and School of Chemistry, UNSW Sydney 2052 Australia 2School of Physics, UNSW Sydney 2052 Australia 3Australian Centre for Nanomedicine and School of Chemistry, UNSW Sydney 2052 Australia

  

Bioconjugate Chemistry (DOI: 10.1021/bc500310v)

Synthesis and High-Throughput Processing of Polymeric Hydrogels for 3D Cell Culture

Stuart B Lowe, Vincent T G Tan, Alexander H Soeriyadi, Thomas P Davis?§#, and J Justin Gooding*?

bc-2014-00310v 0006

 

 

3D cell cultures have drawn a large amount of interest in the scientific community with their ability to closely mimic physiological conditions. Hydrogels have been used extensively in the development of extracellular matrix (ECM) mimics for 3D cell culture. Compounds such as collagen and fibrin are commonly used to synthesize natural ECM mimics; however they suffer from batch-to-batch variation. In this Review we explore the synthesis route of hydrogels; how they can be altered to give different chemical and physical properties; how different biomolecules such as arginylglycylaspartic acid (RGD) or vascular endothelial growth factor (VEGF) can be incorporated to give different biological cues; and how to create concentration gradients with UV light. There will also be emphasis on the types of techniques available in high-throughput processing such as nozzle and droplet-based biofabrication, photoenabled biofabrication, and microfluidics. The combination of these approaches and techniques allow the preparation of hydrogels which are capable of mimicking the ECM.

School of Chemistry and Australian Centre for NanoMedicine, University of New South Wales Sydney NSW 2052 Australia ?ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Parkville VIC 3052 Australia §Department of Chemistry University of Warwick Coventry CV4 7AL United Kingdom #Monash Institute of Pharmaceutical Sciences, Monash University Parkville VIC 3052 Australia
 

Journal of Solid State Electrochemistry (DOI: 10.1007/s10008-014-2606-9). 

Protein sensors based on reversible π–π stacking on basal plane HOPG electrodes

Na Kong, J Justin Gooding, Jingquan Liu

soldstateelectrochemistry

In this study, the modification of basal planes of highly oriented pyrolytic graphite (HOPG) electrodes with pyrene-functionalised biotin (PFB), via π–π stacking, and ethylene glycol antifouling molecules, via covalent bonding, for detection of streptavidin is presented. Biotin was first conjugated to the pyrene moieties by an esterification reaction in order to enable the self-assembly of biotin onto the surface of HOPG via non-covalent π–π stacking. The as-prepared biotinylated electrode was used as the sensing probe to analyze the concentration of streptavidin via the diminution in pyrene electrochemistry resulted from the desorption of pyrene from the surface that is mediated by the biotin–streptavidin recognition. X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), square wave voltammetry (SWV) measurements, and electrochemical impedance spectroscopy (EIS) were used to characterize the amount of surface bound pyrene modified biotin and the concentration of streptavidin. This simple strategy can be applied to the detection of other biomolecules via bio-recognition and the reversible π–π stacking process.

N. Kong : J. Liu.  College of Chemical Science and Engineering, Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071 China.  J J Gooding. School of Chemistry and the Australian Centre for Nano Medicine, UNSW Sydney NSW 2052 Australia

   

Langmuir (DOI: 10.1007/s10008-014-2606-9). 

An Efficient and Highly Versatile Synthetic Route to Prepare Iron Oxide Nanoparticles/Nanocomposites with Tunable Morphologies

Bunyamin Karagoz§, Jonathan Yeow, Lars Esser, Shyam M Prakash, Rhiannon P Kuchel, Thomas P Davis*#, and Cyrille Boyer*

 Abstract Image

We report a versatile synthetic method for the in situ self-assembly of magnetic-nanoparticle-functionalized polymeric nanomorphologies, including spherical micelles and rod-like and worm-like micelles and vesicles. Poly(oligoethylene glycol methacrylate)-block-(methacrylic acid)-block-poly(styrene) (POEGMA-b-PMAA-b-PST) triblock copolymer chains were simultaneously propagated and self-assembled via a polymerization-induced self-assembly (PISA) approach. Subsequently, the carboxylic acid groups in the copolymers were used to complex an iron ion (FeII/FeIII) mixture. Iron oxide nanoparticles were then formed in the central block, within the polymeric nanoparticles, via alkaline coprecipitation of the iron(II) and (III) salts. Nanoparticle morphologies, particle sizes, molecular weights, and chemical structures were then characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), size exclusion chromatography (SEC), and 1H NMR measurements. TEM micrographs showed that the average size of the magnetic nanoparticles was ∼7 nm at the hydrophobic/hydrophilic nexus contained within the nanoparticles. In addition, XRD was used to confirm the formation of iron oxide nanoparticles. Importantly, the polymeric nanoparticle morphologies were not affected by the coprecipitation of the magnetic nanoparticles. The hybrid nanoparticles were then evaluated as negative MRI contrast agents, displaying remarkably high transverse relaxivities (r2, greater than 550 mM–1 s–1 at 9.4 T); a result, that we hypothesize, ensues from iron oxide nanoparticle clustering at the hydrophobic–hydrophilic interface. This simple synthetic procedure is highly versatile and produces nanocarriers of tunable size and shape with high efficacy as MRI contrast agents and potential utility as theranostic delivery vectors.

Centre for Advanced Macromolecular Design, School of Chemical Engineering, University of New South Wales, Sydney NSW 2052 Australia Australian Centre for NanoMedicine, School of Chemical Engineering, The University of New South Wales, Sydney NSW 2052 Australia §Department of Chemistry, Istanbul Technical University, Maslak 34469 Istanbul Turkey Electron Microscope Unit, Mark Wainwright Analytical Centre, School of Chemical Engineering, University of New South Wales, Sydney NSW 2052 Australia ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne VIC 3052 Australia #Department of Chemistry, University of Warwick, Coventry CV4 7AL UK
 

Bioorganic and Medicinal Chemistry (DOI: 10.1016/j.bmc.2014.08.010)

Synthesis, anti-cancer and anti-inflammatory activity of novel 2-substituted isoflavenes

Eleanor Eiffea,Eddy Pasquierb, c, Maria Kavallarisb, d, Cristan Herberte, David StC Blacka, Naresh Kumara

Fifteen novel 2-substituted isoflavenes were synthesised via nucleophilic addition to isoflavylium salts. Twelve of the newly synthesised isoflavenes, along with the unsubstituted parent isoflavene, were tested in cell viability assays against the SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines. While the 2-substituted isoflavenes displayed a range of anti-proliferative activities, in most cases they were less active that the unsubstituted isoflavene (IC50=9.9μM vs SHEP; IC50=33μM vs MDA-MB-231). However, compound 7f, derived from the reaction between isoflavylium salt 5 and para-methoxyacetophenone, showed improved anti-proliferative activity against breast cancer cells (IC50=7.6μM). Furthermore, compound 7f, as well as analogues 7a, 7c, 11d and 14, inhibited the production of interleukin-6 in LPS-activated RAW 264.7 cells.

aSchool of Chemistry, UNSW Sydney NSW 2052 Australia bChildren’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, UNSW Randwick NSW 2052 Australia cMetronomics Global Health Initiative, Marseille, France dAustralian Centre for Nanomedicine, School of Chemical Engineering UNSW, Sydney New South Wales 2052 Australia eSchool of Medical Sciences, The University of New South Wales Sydney NSW 2052 Australia

 
 

RSC Advances (DOI 10.1039/C4RA03331K).

Novel functional cisplatin carrier based on carbon nanotubes–quercetin nanohybrid induces synergistic anticancer activity against neuroblastoma in vitro

Orazio Vittorioab†, Miriam Brandla, Giuseppe Cirillocd†*, Umile Gianfranco Spizzirric, Nevio Piccic, Maria Kavallarisab, Francesca Iemmac, Silke Hampeld

rscadvancesjuly2014

The synergistic effects of a three-functional hybrid material composed by methacrylic acid (MAA), quercetin (Q) and carbon nanotubes (CNTs), with cisplatin (CP) was evaluated in human neuroblastoma cells. A three-functional hybrid material suitable for CP combination therapy was synthesized through the free radical-induced reaction between methacrylic acid, quercetin and carbon nanotubes. Two-functional materials were prepared and fully characterized by coupling CNTs and MAA, as well as MAA and Q. Folin-Ciocalteu assay was used to assess the functionalization degree expressed as mg of Q per gram of materials and we found to be 2.33 for CNTs_PMAA_Q and 2.01 for PMAA_Q. The anticancer activity of CNTs_PMAA_Q was observed in human neuroblastoma cells by determination of cells’ proliferation using an Alamar blue assay. Successively, cells were treated with a combination of CP and the nanocomposite showing strong synergistic anti-cancer effects in neuroblastoma cells. These studies showed that nanoparticles formulation incorporating quercetin and carbon nanotubes are good candidates for CP synergistic treatment against neuroblastoma.

aChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, NSW, Australia bAustralian Centre for NanoMedicine, University of New South Wales NSW Australia cDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria Rende (CS) Italy dLeibniz Institute for Solid State and Materials Research Dresden, Dresden Germany.

 
 

Advanced Healthcare Materials (DOI: 10.1002/adhm.201400164).

Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity

Yang Li1,2, Hien T T Duong2, Sophie Laurent3, Alexandre MacMillan4, Renee Megan Whan4, Luce Vander Elst3, Robert N Muller3,5, Jinming Hu6, Andrew Lowe1, Cyrille Boyer1,2*, Thomas P Davis6,7

advancedhealthercarematerials

Dual-functional star polymers (diameters 15 nm) are synthesized producing nanoparticles with excellent colloidal stability in both water and serum. The nanoparticles are built with aldehyde groups in the core and activated esters in the arms. The different reactivity of the two functional groups to sequentially react with different amino compounds is exploited; doxorubicin (DOX) and 1-(5-amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DO3A-tBu-NH2)—a chelating agent effective for the complexation of Gadolinium ions (Gd). The activated ester group is employed to attach the DO3A chelating agent, while the aldehyde groups are exploited for DOX conjugation, providing a controlled release mechanism for DOX in acidic environments. DOX/Gd-loaded nanoparticles are rapidly taken up by MCF-7 breast cancer cells, subsequently releasing DOX as demonstrated using in vitro fluorescence lifetime imaging microscopy (FLIM). Endosomal, DOX release is observed, using a phasor plot representation of the fluorescence lifetime data, showing an increase of native DOX with time. The MRI properties of the stars are assessed and the relaxivity of Gd loaded in stars is three times higher than conventional organic Gd/DO3A complexes. The DOX/Gd-conjugated nanoparticles yield a similar IC50 to native DOX for breast cancer cell lines, confirming that DOX integrity is conserved during nanoparticle attachment and release.

1Centre for Advanced Macromolecular Design, School of Chemical Engineering, University of New South Wales, Sydney NSW Australia 2Australian Centre for Nanomedicine, School of Chemical Engineering, University of New South Wales, Sydney NSW Australia 3NMR and Molecular Imaging Laboratory, Department of General, Organic and Biomedical Chemistry, University of Mons, Mons Belgium 4Biomedical Imaging Facility, University of New South Wales, Sydney NSW Australia 5CMMI – Center of Microscopy and Molecular Imaging, Gosselies Belgium 6ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville VIC Australia 7Department of Chemistry, University of Warwick, Coventry UK

 

Journal of Physical Chemistry B (DOI: 10.1021/jp504564s).

Thermodynamic Factors Impacting the Peptide-Driven Self-Assembly of Perylene Diimide Nanofibers

Galen L Eakins†‡, Joseph K Gallaher†‡, Robert A Keyzers, Alexander Falber⊥∥, James E A Webb, Alistair Laos, Yaron Tidhar§, Haim Weissman§, Boris Rybtchinski§, Pall Thordarson, and Justin M Hodgkiss*†‡

journalofphysicalchemistry

Synthetic peptides offer enormous potential to encode the assembly of molecular electronic components, provided that the complex range of interactions is distilled into simple design rules. Here, we report a spectroscopic investigation of aggregation in an extensive series of peptide-perylene diiimide conjugates designed to interrogate the effect of structural variations. By fitting different contributions to temperature dependent optical absorption spectra, we quantify both the thermodynamics and the nature of aggregation for peptides by incrementally varying hydrophobicity, charge density, length, as well as asymmetric substitution with a hexyl chain, and stereocenter inversion. We find that coarse effects like hydrophobicity and hexyl substitution have the greatest impact on aggregation thermodynamics, which are separated into enthalpic and entropic contributions. Moreover, significant peptide packing effects are resolved via stereocenter inversion studies, particularly when examining the nature of aggregates formed and the coupling between π electronic orbitals. Our results develop a quantitative framework for establishing structure–function relationships that will underpin the design of self-assembling peptide electronic materials.

MacDiarmid Institute for Advanced Materials and Nanotechnology, School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600 Wellington 6012 New Zealand School of Chemistry and the Australian Centre for NanoMedicine, University of New South Wales Sydney NSW 2052 Australia Flurosol Industries Pty Ltd, Level 5 574 St Kilda Road Melbourne VIC 3004 Australia §Department of Organic Chemistry, Weizmann Institute of Science, Rehovot 76100 Israel

 

Chemical Science (DOI: 10.1039/C4SC01309C).

Aqueous photoinduced living/controlled polymerization: tailoring for bioconjugation

Jiangtao XuKenward Jung, Nathaniel Alan Corrigan, Cyrille Boyer

chemicalsciencediagram

 

We report a photoinduced living polymerization technique able to polymerize a large range of monomers, including methacrylates, acrylates and acrylamides, in water and biological media as well as organic solvents. This polymerization technique employs ultra-low concentrations of a ruthenium-based photoredox catalyst (typically 1 ppm to monomers) and enables low energy visible LED light to afford well-defined polymers with narrow polydispersities (Mw/Mn < 1.3). In this paper, different parameters, including photocatalyst concentrations and solvent effects, were thoroughly investigated. In addition, successful polymerizations in biological media have been reported with good control of the molecular weights and molecular weight distributions (Mw/Mn < 1.4). Finally, protein–polymer bioconjugates using a “grafting from” approach were demonstrated using bovine serum albumin as a model biomacromolecule. The enzymatic bioactivity of the protein was demonstrated to be maintained using a standard assay.

Centre for Advanced Macromolecular Design and Australian Centre for NanoMedicine, School of Chemical Engineering, University of New South Wales, Sydney Australia

 
 

Porous Silicon for Biomedical Application (DOI: 10.1533/9780857097156.1.81).

Modifying porous silicon with self-assembled monolayers for biomedical applications

JJ Gooding and Y Zhu

 

Many biomedical applications of porous silicon (PSi) require the surface of the material to be modified such that it interfaces with the biological system in a controlled way. This is particularly true if PSi is to be used for biosensing. There have been a number of strategies for modifying PSi, including polymers, oxidation and a variety of different self-assembled monolayer systems. Herein is reviewed the modification strategies that employ self-assembled monolayers, including a discussion of their advantages and disadvantages. Monolayer strategies for modifying PSi fall typically into two categories. In the first category, PSi is oxidized and reacted with organosilanes. In the second category, hydrogen-terminated PSi surfaces are reacted with molecules that possess terminal alkenes and alkynes, which is referred to as a hydrosilylation reaction. Both methods are covered in detail in this chapter, along with strategies for introducing multiple chemical functionalities on the PSi surfaces.

Australian Centre for NanoMedicine, School of Chemistry, University of New South Wales, Sydney Australia

 

Langmuir (DOI: 10.1021/la501774b)

 

 

Biointerfaces on Indium–Tin Oxide Prepared from Organophosphonic Acid Self-Assembled Monolayers

Muthukumar Chockalingam†‡, Astrid Magenau†§, Stephen G Parker†‡, Maryam Parviz†‡, S R C Vivekchand†‡, Katharina Gaus†§, J Justin Gooding*†‡

 

langmuirjune2014
 

Herein we show the development of biointerfaces on indium–tin oxide (ITO) surfaces prepared from organophosphonate self-assembled monolayers. The interfaces were prepared in a stepwise fabrication procedure containing a base monolayer modified with oligo(ethylene oxide) species to which biological recognition ligands were attached. The density of ligands was controlled by varying the ratio of two oligo(ethylene oxide) species such that only one is compatible with further coupling. The final biointerface on ITO was assessed using cell adhesion studies, which showed that the biointerfaces prepared on ITO performed similarly to equivalent monolayers on gold or silicon.

Australian Centre for NanoMedicine, School of Chemistry, §Centre for Vascular Research, and ARC Centre of Excellence in Coherent Bio-Nano Science and Technology, University of New South Wales, Sydney 2052 Australia
 

Macromolecules (DOI: 10.1021/ma500883y)

Oxygen Tolerance Study of Photoinduced Electron Transfer–Reversible Addition–Fragmentation Chain Transfer (PET-RAFT) Polymerization Mediated by Ru(bpy)3Cl2

Jiangtao Xu*, Kenward Jung, Cyrille Boyer*

macromoleculesjune2014

This study reports a highly efficient photoredox catalyst, Ru(bpy)3Cl2, capable of controlling the polymerization of methacrylates, acrylates, and acrylamides in the presence of thiocarbonylthio compounds via a photoinduced electron transfer–reversible addition–fragmentation chain (PET-RAFT) process. This polymerization technique was performed in a closed vessel in the presence or absence of air. Online Fourier transform near-infrared spectroscopy (FTNIR) was employed to monitor the monomer conversions of methyl methacrylate, methyl acrylate, and N,N?-dimethylacrylamide in the presence or absence of air. Interestingly, after an induction period, the polymerization proceeded in the presence of air to yield well-defined polymers (PDI < 1.20). The polymers were characterized by 1H NMR, UV–vis spectroscopy, and gel permeation chromatography. Excellent end-group retention was also demonstrated by NMR, UV–vis, and successive chain extensions of the resulting homopolymers to yield diblock and multiblock copolymers (decablock copolymers).

 Centre for Advanced Macromolecular Design and Australian Centre for NanoMedicine, School of Chemical Engineering, UNSW Australia, Sydney NSW 2052 Australia

 

Molecular Oncology (DOI: 10.1016/j.molonc.2014.06.007).

Computational analysis of image-based drug profiling predicts synergistic drug combinations: Applications in triple-negative breast cancer

Miriam B Brandlabc, Eddy Pasquierad, Fuhai Lic, Dominik Becke, Sufang Zhangc, Hong Zhaoc1, Maria Kavallarisaf12, , Stephen TC Wongc2

 

An imaged-based profiling and analysis system was developed to predict clinically effective synergistic drug combinations that could accelerate the identification of effective multi-drug therapies for the treatment of triple-negative breast cancer and other challenging malignancies. The identification of effective drug combinations for the treatment of triple-negative breast cancer (TNBC) was achieved by integrating high-content screening, computational analysis, and experimental biology. The approach was based on altered cellular phenotypes induced by 55 FDA-approved drugs and biologically active compounds, acquired using fluorescence microscopy and retained in multivariate compound profiles. Dissimilarities between compound profiles guided the identification of 5 combinations, which were assessed for qualitative interaction on TNBC cell growth. The combination of the microtubule-targeting drug vinblastine with KSP/Eg5 motor protein inhibitors monastrol or ispinesib showed potent synergism in 3 independent TNBC cell lines, which was not substantiated in normal fibroblasts. The synergistic interaction was mediated by an increase in mitotic arrest with cells demonstrating typical ispinesib-induced monopolar mitotic spindles, which translated into enhanced apoptosis induction. The antitumour activity of the combination vinblastine/ispinesib was confirmed in an orthotopic mouse model of TNBC. Compared to single drug treatment, combination treatment significantly reduced tumour growth without causing increased toxicity. Image-based profiling and analysis led to the rapid discovery of a drug combination effective against TNBC in vitro and in vivo, and has the potential to lead to the development of new therapeutic options in other hard-to-treat cancers.

 aChildren’s Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick NSW Australia bSchool of Engineering and Information Technology, University of New South Wales, Canberra ACT 2600 Australia cDepartment of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston TX 77030 USA dMetronomics Global Health Initiative, Marseille France eLowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney Australia fARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, University of New South Wales, NSW 2052 Australia

 

ACS Macro Letters (DOI:  10.1021/mz500245k).

Combining Enzymatic Monomer Transformation with Photoinduced Electron Transfer − Reversible Addition–Fragmentation Chain Transfer for the Synthesis of Complex Multiblock Copolymers

Changkui Fu, Jiangtao Xu, Lei Tao*, Cyrille Boyer*

ACS Macro Letters

A novel and facile method, involving enzymatic monomer synthesis and a photocontrolled polymerization technique, has been successfully employed for the preparation of high-order multiblock copolymers. New acrylate monomers were synthesized via enzymatic transacylation between an activated monomer, ie 2,2,2-trifluoroethyl acrylate (TFEA), and various functional alcohols. These synthesized monomers were successfully polymerized without further purification via photoinduced electron transfer–reversible addition–fragmentation chain transfer (PET-RAFT) polymerization under low energy blue LED light (4.8 W) in the presence of an iridium-based photoredox catalyst (fac-[Ir(ppy)3]). In this condition, PET-RAFT allows us to achieve high monomer conversion (100%) with excellent integrity of the end group (>80%). Different multiblock (co)polymers, including poly(hexyl acrylate) pentablock homopolymer, poly(methyl acylate-b-ethyl acrylate-b-n-propyl acrylate-b-n-butyl acrylate-b-n-pentyl acrylate) pentablock copolymer, and poly(3-oxobutyl acrylate-b-methyl acrylate-b-3-(trimethylsilyl)prop-2-yn-1-yl acrylate) triblock copolymer containing functional groups were rapidly prepared via sequential addition of monomers without purification steps.

The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 PR China Centre for Advanced Macromolecular Design, School of Chemical Engineering, and Australian Centre for NanoMedicine, School of Chemical Engineering, UNSW Australia Sydney NSW 2052 Australia
 

ACS Macro Letters (DOI: 10.1021/mz500195u).

In Situ Formation of Polymer–Gold Composite Nanoparticles with Tunable Morphologies

Richard Bleach, Bunyamin Karagoz§, Shyam M Prakash, Thomas P Davis, Cyrille Boyer

 acsjune102014

 

A simple and efficient route to gold–polymer nanoparticle composites is described. Our versatile synthetic route exerts facile control over polymer nanoparticle morphology, including micelles, rod-like structures, and vesicles, all easily attainable from a single polymerization taken to different monomer conversions. Specifically, poly[oligo(ethylene glycol) methacrylate]-b-poly(dimethylaminoethyl methacrylate)-b-poly(styrene) (POEGMA-b-PDMAEMA-b-PST) triblock copolymers were synthesized using a polymerization induced self-assembly (PISA) approach. Subsequently, spherical gold nanoparticles (10 nm AuNPs) were formed at the hydrophilic–hydrophobic nexus of the assembled triblock copolymer nanoaggregates by the addition of chloroauric acid (HAuCl4) followed by in situ reduction using NaBH4. After reduction, the cloudy white nanoparticle dispersions turned to a red-purple color. The gold nanoparticles that formed were stabilized by the enveloping polymeric nanostructures, neither precipitation nor agglomeration occurred. We demonstrated that we were able to tune the gold nanoparticle composition in these polymer–gold composites by varying the concentration of chloroauric acid. Morphology, particle size, molecular weight, AuNP content, and chemical structure of the polymer structures were characterized by transmittance electron microscopy (TEM), dynamic light scattering (DLS), size exclusion chromatography (SEC), thermal gravimetric analysis (TGA), and 1H NMR. Finally, the formation of the AuNPs occurred without affecting the polymer nanoparticle morphology.

Centre for Advanced Macromolecular Design, School of Chemical Engineering, University of New South Wales, Sydney NSW 2052 Australia Australian Centre for Nanomedicine, University of New South Wales, Sydney NSW 2052 Australia §Istanbul Technical University Department of Chemistry, Maslak 34469 Istanbul Turkey ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University Parkville VIC 3052 Australia Department of Chemistry, University of Warwick, Coventry CV4 7AL United Kingdom

 
 

BioMacromolecules (DOI: 10.1021/bm500422v)

Nanoparticle (Star Polymer) Delivery of Nitric Oxide Effectively Negates Pseudomonas aeruginosa Biofilm Formation 

Hien T T Duong, Kenward Jung, Samuel K Kutty§, Sri Agustina, Nik Nik M Adnan, Johan S Basuki, Naresh Kumar§, Thomas P Davis*#, Nicolas Barraud*, Cyrille Boyer*

biomacromoleculesjune2014diagram

Biofilms are increasingly recognized as playing a major role in human infectious diseases, as they can form on both living tissues and abiotic surfaces, with serious implications for applications that rely on prolonged exposure to the body such as implantable biomedical devices or catheters. Therefore, there is an urgent need to develop improved therapeutics to effectively eradicate unwanted biofilms. Recently, the biological signaling molecule nitric oxide (NO) was identified as a key regulator of dispersal events in biofilms. In this paper, we report a new class of core cross-linked star polymers designed to store and release nitric oxide, in a controlled way, for the dispersion of biofilms. First, core cross-linked star polymers were prepared by reversible addition–fragmentation chain transfer polymerization (RAFT) via an arm first approach. Poly(oligoethylene methoxy acrylate) chains were synthesized by RAFT polymerization, and then chain extended in the presence of 2-vinyl-4,4-dimethyl-5-oxazolone monomer (VDM) with N,N-methylenebis(acrylamide) employed as a cross-linker to yield functional core cross-linked star polymers. Spermine was successfully attached to the star core by reaction with VDM. Finally, the secondary amine groups were reacted with NO gas to yield NO-core cross-linked star polymers. The core cross-linked star polymers were found to release NO in a controlled, slow delivery in bacterial cultures showing great efficacy in preventing both cell attachment and biofilm formation in Pseudomonas aeruginosa over time via a nontoxic mechanism, confining bacterial growth to the suspended liquid.

Australian Centre for Nanomedicine and Centre for Advanced Macromolecular Design, School of Chemical Engineering, §School of Chemistry, and Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW Australia 2052  ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Melbourne Victoria Australia 3052 #Department of Chemistry, University of Warwick, Coventry CV4 7AL United Kingdom

 
 

Angewandte Chemie (DOI: 10.1002/anie.201403147).

Biomimetic Polymers Responsive to a Biological Signaling Molecule: Nitric Oxide Triggered Reversible Self-assembly of Single Macromolecular Chains into Nanoparticles

Jinming Hu1, Michael R Whittaker1, Hien Duong3, Yang Li1, Cyrille Boyer3* Thomas P Davis12*

thumbnail image

Novel nitric oxide (NO) responsive monomers (NAPMA and APUEMA) containing o-phenylenediamine functional groups have been polymerized to form NO-responsive macromolecular chains as truly biomimetic polymers. Upon exposure to NO—a ubiquitous cellular signaling molecule—the NAPMA- and APUEMA-labeled thermoresponsive copolymers exhibited substantial changes in solubility, clearly characterized by tuneable LCST behavior, thereby inducing self-assembly into nanoparticulate structures. Moreover, the NO-triggered self-assembly process in combination with environmentally sensitive fluorescence dyes could be employed to detect and image endogenous NO.

J Hu, M R Whittaker, Y Li, TP Davis ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences Monash University, Parkville VIC 3052 Australia TP Davis Chemistry Department, University of Warwick Coventry, ULCV4 7AL (UK) H Duong, C Boyer Australian Centre for NanoMedicine School of Chemical Engineering, University of New South Wales Sydney NSW 2052 Australia

 

 Bioconjugate Chemistry (DOI: 10.1021/bc500144u)

Antibody Modified Porous Silicon Microparticles for the Selective Capture of Cells

Bin Guan, Astrid Magenau, Simone Ciampi, Katharina Gaus, Peter J Reece, J Justin Gooding*§

bioconjugatediagram

Herein, the ability of porous silicon (PSi) particles for selectively binding to specific cells is investigated. PSi microparticles with a high reflectance band in the reflectivity profile are fabricated, and subsequently passivated and modified with antibodies via the Cu(I)-catalyzed alkyne–azide cycloaddition reaction and succimidyl activation. To demonstrate the ability of the antibody-modified PSi particles to selectively bind to one cell type over others, HeLa cells were transfected with surface epitopes fused to fluorescent proteins. The antibody-functionalized PSi particles showed good selectivity for the corresponding surface protein on HeLa cells, with no significant cross-reactivity. The results are important for the application of PSi particles in cell sensing and drug delivery.

School of Chemistry, The Australian Centre for NanoMedicine, §ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Centre for Vascular Research, and School of Physics, University of New South Wales, Sydney Australia 2052

 

Biosensors and Bioelectronics. (DOI 10.1016/j.bios.2014.05.039)

Brief review of monitoring methods for loop-mediated isothermal amplification (LAMP)

Xuzhi Zhanga, Stuart B Loweb, John Justin Goodingb

 The loop-mediated isothermal amplification (LAMP) technique has the potential to revolutionize molecular biology because it allows DNA amplification under isothermal conditions and is highly compatible with point-of-care analysis. To achieve efficient genetic analysis of samples, the method of real-time or endpoint determination selected to monitor the biochemical reaction is of great importance. In this paper we briefly review progress in the development of monitoring methods for LAMP.

 aYellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture, Qingdao 266071 PR China bSchool of Chemistry and Australian Centre for NanoMedicine, University of New South Wales Sydney NSW 2052 Australia

 

Chemical Communications. (DOI: 10.1039/C4CC03418J).

A robust DNA interface on a silicon electrode

Pauline Michaels,a Muhammad Tanzirul Alam,a Simone Ciampi,a  William Rouesnel,a Stephen G Parker,ab  Moinul H Choudhurya J Justin Gooding*abc

 
chemicalcommunicationmay2014diagram

Two different interfaces prepared via UV-hydrosilylation of undecylenic acid and 1,8-nonadiyne on silicon(111) have been explored to develop a robust electrochemical DNA sensor. Electrodes modified with undecylenic acid were found to stably immobilise DNA but could not resist the growth of insulating oxides, whereas 1,8-nonadiyne modified electrodes satisfy both requirements.

aSchool of Chemistry, The University of New South Wales, Sydney, Australia bAustralian Centre for NanoMedicine, University of New South Wales, Sydney Australia cARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, Sydney Australia

 

Electroanalysis (DOI: 10.1002/elan.201400102).

Investigation of the Antifouling Properties of Phenyl Phosphorylcholine-Based Modified Gold Surfaces 

Maryam Parviz,[a] Nadim Darwish,[a] Muhammad Tanzirul Alam,[a] Stephen G Parker,[a] Simone Ciampi,[a] J Justin Gooding*[a] 

 electroanalysismay2014diagram

Low impedance, antifouling coatings on gold electrodes based on three new zwitterionic phenyl phosphorylcholine (PPC)-based layers namely 1) reductively adsorbed PPC diazonium salt, 2) dithiocarbamate PPC SAM and 3) lipoamide PPC SAM (PPC coupled to ?-lipoic acid) were evaluated. The layers were assessed for their ability to limit nonspecific adsorption of proteins to electrode surface with some significant differences observed compared with previously studied PPC diazonium salts reductively adsorbed on glassy carbon. Fluorescence microscopy and electrochemical impedance spectroscopy results suggest that protein adsorption is sensitive to the difference in the structure of the PPC molecules and the charge neutrality of the layers. The lipoamide PPC SAM was shown to be the most effective at resisting nonspecific protein adsorption and this layer was as effective as the ‘gold standard’ of oligo(ethylene oxide) SAMs on gold and PPC diazonium salts reductively adsorbed on glassy carbon.

M Parviz, N Darwish, MT Alam, SG Parker, S Ciampi, JJ Gooding School of Chemistry and Australian Centre for NanoMedicine, University of New South Wales Sydney, NSW 2052 Australia

 

 Nature Cell Biology (doi:10.1038/ncb2970)

Galectin-3 drives glycosphingolipid-dependent biogenesis of clathrin-independent carriers

Ramya Lakshminarayan1,2,3,9,10, ChristianWunder1,2,3,9,10, Ulrike Becken1,2,3,9,10,Mark T. Howes4, Carola Benzing5,Senthil Arumugam1,2,3, Susanne Sales6, Nicholas Ariotti4, Valérie Chambon1,2,3,10, Christophe Lamaze2,3,7,10, Damarys Loew8, Andrej Shevchenko6, Katharina Gaus5, Robert G Parton4,11 and Ludger Johannes1,2,3,10,11 

 naturecellbiologyimage

Several cell surface molecules including signalling receptors are internalized by clathrin-independent endocytosis. How this process is initiated, how cargo proteins are sorted and membranes are bent remains unknown. Here, we found that a carbohydrate-binding protein, galectin-3 (Gal3), triggered the glycosphingolipid (GSL)-dependent biogenesis of a morphologically distinct class of endocytic structures, termed clathrin-independent carriers (CLICs). Super-resolution and reconstitution studies showed that Gal3 required GSLs for clustering and membrane bending. Gal3 interacted with a defined set of cargo proteins. Cellular uptake of the CLIC cargo CD44 was dependent on Gal3, GSLs and branched N-glycosylation. Endocytosis of β1-integrinwas also reliant on Gal3. Analysis of different galectins revealed a distinct profile of cargoes and uptake structures, suggesting the existence of different CLIC populations. We conclude that Gal3 functionally integrates carbohydrate specificity on cargo proteins with the capacity of GSLs to drive clathrin-independent plasma membrane bending as a first step of CLIC biogenesis.

1Institut Curie—Centre de Recherche, Endocytic Trafficking and Therapeutic Delivery group, 26 rue d’Ulm, 75248 Paris Cedex 05 France 2CNRS UMR3666, 75005 Paris France 3INSERM U1143 75005 Paris France 4Institute for Molecular Bioscience, University of Queensland St Lucia QLD 4072 Australia 5Centre for Vascular Research, Australian Centre for Nanomedicine and ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales Sydney NSW 2052 Australia 6Max Planck Institute of Molecular Cell Biology and Genetics Pfotenhauerstr 108 01307 Dresden Germany 7Institut Curie—Centre deRecherche, Membrane Dynamics and Mechanics of Intracellular Signaling group, 26 rue d’Ulm 75248 Paris Cedex 05 France 8Institut Curie—Centre de Recherche, Proteomics and Mass Spectrometry Laboratory 26 rue d’Ulm 75248 Paris Cedex 05 France 9These authors contributed equally to this work. 10Authors were previously members of UMR144 CNRS.

 

 Current Opinion in Chemical Biology (DOI: 10.1016/j.cbpa.2014.04.009).

The organisation of the cell membrane: do proteins rule lipids? 

Jérémie Rossy, Yuanqing Ma, Katharina Gaus

 

currebiologydiagram

Cell membranes are a complex adaptive system: they are constantly re-organised in response to extra- and intracellular inputs and their local and global structure ultimately determines how, where and when these inputs are processed. This requires a tight coupling of signalling and membranes in localised and specialised compartments. While lipids are essential components of cell membranes, they mostly lack a direct link to the input signals. Here we review how proteins can deform locally membranes, modify and reorganise lipids to form membrane domains and regulate properties like membrane charges and diffusion. From this point-of-view, it appears that proteins play a central role in regulating membrane organisation.

Centre for Vascular Research and Australian Centre for Nanomedicine, University of New South Wales, Sydney Australia

 

 Journal of Polymer Science: Part A Polymer Chemistry (DOI: 10.1002/pola.27220)

Synthesis of complex macromolecules using iterative copper(0)-mediated radical polymerization

Cyrille Boyer1,*, Per B Zetterlund1,* Michael R Whittaker2

 Journal of Polymer Science Part A: Polymer Chemistry

Copper(0) mediated radical polymerization is an efficient and versatile polymerization technique which allows the control of acrylates and methacrylates with an unprecedented maintenance of end group fidelity (∼100%) during the polymerization. In this highlight, we summarize recent works using Cu(0)-mediated radical polymerization for the synthesis of multiblock copolymers via an iterative approach. This approach has been successfully implemented for the synthesis of decablock copolymers, constituted of blocks with a degree of polymerization ranging from 3–4 to 100 units as well as for the preparation of multiblock star polymers. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2083–2098

1Centre for Advanced Macromolecular Design, School of Chemical Engineering, University of New South Wales, Australia 2ARC Centre of Excellence in Convergent Nano-Bio Science & Technology Monash University Parkville Melbourne Australia

  
 

Nanomedicine Nanotechnology Biology and Medicine (doi:10.1016/j.nano.2014.04.012). 

Drug delivery: Beyond active tumour targeting

Sharon M Sagnella, PhD, Joshua A McCarroll, PhD, Maria Kavallaris, PhD

 

nanomedicinediagram

Despite improvements in our understanding of cancer and the concept of personalised medicine, cancer is still a major cause of death. It is established that solid tumours are highly heterogeneous, with a complex tumour microenvironment. Indeed, the tumour microenvironment is made up of a collection of immune cells, cancer-activated fibroblasts, and endothelial cells and in some cases a dense extracellular matrix. Accumulating evidence shows that the tumour microenvironment is a major barrier for the effective delivery of therapeutic drugs to tumour cells. Importantly, nanotechnology has come to the forefront as highly effective delivery vehicles for therapeutic agents. This perspective will discuss how nanomedicine can be used to target and deliver therapeutic drugs specifically to tumour cells. Moreover, emerging opportunities to modulate the tumour microenvironment and increase the delivery and efficacy of chemotherapy agents to solid tumours will be highlighted.

Australian Centre for NanoMedicine, University of New South Wales, Sydney NSW 2052 Australia

  
 

Electroanalysis (10.1002/elan.201400097)

Approaches Toward Allowing Electroanalytical Devices to be Used in Biological Fluids

Abbas Barfidokht, J Justin Gooding*

 

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Biofouling on surfaces can deleteriously affect the function of electrochemical sensor used in a biological fluid. The demand is thus to develop a sensor operatable in complex matrices. Herein, we concisely review the technologies developed to date to minimize fouling of electrochemical interfaces by blood-based fluids with an emphasis on affinity biosensing. The methods toward this sensor fabrication that are discussed here include approaches where; chemically modified surfaces with antifouling layers such as ethylene oxides, zwitterionics and some alternative antifouling agents; physical forces such as fluidic systems; electrode surface topography, prevent biofouling, as well as recent approaches where biofouling does not interfere with the response (aptasensors). Furthermore, the important emerging field of implantable biosensors, originated from such fabrication procedures is discussed.

*School of Chemistry and Australian Centre for NanoMedicine, University of New South Wales, Sydney NSW 2052 Australia

  
 

Journal of Polymer Science Part A: Polymer Chemistry (DOI: 10.1002/pola.27221)

Organic nitrate functional nanoparticles for the glutathione-triggered slow-release of nitric oxide

Hien T T Duong1, Amy Ho2, Thomas P Davis3,4,*, Cyrille Boyer1,2,*

 

polymerchemistry4may14

Nitrate-containing amphiphilic block copolymer chains were self-assembled into micellar nanostructures as a reservoir for the slow-release delivery of nitric oxide (NO). Poly(oligo(ethylene glycol) methyl ether methacrylate)-block-poly(vinyl benzyl chloride-co-styrene) was prepared by reversible addition fragmentation chain transfer (RAFT) polymerization. Pendant chloro- groups in the polymer backbone were reacted with silver nitrate (AgNO3) to introduce nitrate functionality. The nitrate-containing micelles proved to be stable in water, with no detectableNOrelease. The release ofNOwas then triggered by exposure to glutathione, and it was found that 36 and 99% of NO was released at 37 and 60°C, respectively, after 21 h.

1Australian Centre for NanoMedicine, School of Chemical Engineering, University of New South Wales, Sydney Australia 2Centre for Advanced Macromolecular Design, School of Chemical Engineering, University of New South Wales, Sydney Australia 3ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, Monash Institute of Pharmaceutical Sciences, Monash University Parkville, Melbourne 4Department of Chemistry, University of Warwick, United Kingdom

 

Langmuir (dx.doi.org/10.1021/la500945f)

Versatile "click chemistry" approach to functionalizing silicon quantum dots: applications toward fluorescent cellular imaging

Xiaoyu Cheng,†,‡ Stuart B Lowe,†,‡ Simone Ciampi,†,§ Astrid Magenau,?,? Katharina Gaus,‡,? Peter J Reece,# J Justin Gooding*,†,‡

 longmuirapril2014

In this study, we describe a solution procedure for the preparation and surface modification of photostable colloidal silicon quantum dots (SiQDs) for imaging of cancer cells. Photoluminescent SiQDs were synthesized by reduction of halogenated silane precursors using a microemulsion process. It was shown that 1,8-nonadiyne molecules could be grafted onto the surface of hydrogen-terminated SiQDs via ultraviolet (UV)-promoted hydrosilylation, demonstrated by Fourier transform infrared spectroscopy (FTIR) measurements. In addition, various azide molecules were coupled onto nonadiyne-functionalized particles, rendering particles dispersible in selected polar and nonpolar solvents. The photoluminescence of functionalized SiQDs was stable against photobleaching and did not vary appreciably within biologically applicable pH and temperature ranges. To demonstrate compatibility with biological systems, water-soluble SiQDs were used for fluorescent imaging of HeLa cells. In addition, the SiQDs were shown to be non-cytotoxic at concentrations up to 240 μg/mL. The results presented herein provide good evidence for the versatility of functionalized SiQDs for fluorescent bioimaging application.

School of Chemistry, Australian Centre for NanoMedicine, ?Centre for Vascular Research, and #School of Physics, University of New South Wales, Sydney, New South Wales 2052 Australia

  

Frontiers in Physiology (DOI: 10.3389/fphys.2014.00141)

Role of pancreatic stellate cells in chemoresistance in pancreatic cancer

Joshua A McCarroll1,2†, Stephanie Naim3†, George Sharbeen3, Nelson Russia3, Julia Lee3, Maria Kavallaris1,2, David Goldstein3, Phoebe A Phillips3*

 

Pancreatic cancer is highly chemoresistant. A major contributing factor is the characteristic extensive stromal or fibrotic reaction, which comprises up to 90% of the tumor volume. Over the last decade there has been intensive research into the role of the pro-fibrogenic pancreatic stellate cells (PSCs) and their interaction with pancreatic cancer cells. As a result of the significant alterations in the tumor microenvironment following activation of PSCs, tumor progression, and chemoresistance is enhanced. This review will discuss how PSCs contribute to chemoresistance in pancreatic cancer.

1Tumour Biology and Targeting Program, Lowy Cancer Research Centre, Children's Cancer Institute Australia, University of New South Wales, Sydney NSW Australia 2Australian Centre for NanoMedicine, University of New South Wales, Sydney NSW Australia 3Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney NSW Australia

 

Polymer Chemistry (DOI: 10.1039/C4PY00193A)

Photoredox catalyst-mediated atom transfer radical addition for polymer functionalization under visible light

Jiangtao Xu,*a  Amir Atme,a  Ana Flavia Marques Martins,a  Kenward Junga, Cyrille Boyer*a

 polymerchemistryapril2014image

A facile method for post-functionalization of polymers with side olefin groups was developed by visible light-mediated atom transfer radical addition (ATRA) employing a photoredox catalyst, fac-Ir(ppy)3. In this work, various haloalkanes and α-halocarbonyls were introduced via post-modification into the polymer chains. This communication reports the first example of successful post-modification of polymers using a photoredox catalyst.

aCentre for Advanced Macromolecular Design and Australian Centre for NanoMedicine, School of Chemical Engineering, UNSW Australia, Sydney Australia

  

PLoS Biology  (DOI: 10.1371/journal.pbio.1001832)

Endocytic Crosstalk: Cavins, Caveolins, and Caveolae Regulate Clathrin-Independent Endocytosis

Natasha Chaudhary, Guillermo A Gomez, Mark T Howes, Harriet P Lo, Kerrie-Ann McMahon,  James A Rae, Nicole L Schieber, Michelle M Hill, Katharina Gaus, Alpha S Yap, Robert G Parton

 plosdiagram

Several studies have suggested crosstalk between different clathrin-independent endocytic pathways. However, the molecular mechanisms and functional relevance of these interactions are unclear. Caveolins and cavins are crucial components of caveolae, specialized microdomains that also constitute an endocytic route. Here we show that specific caveolar proteins are independently acting negative regulators of clathrin-independent endocytosis. Cavin-1 and Cavin-3, but not Cavin-2 or Cavin-4, are potent inhibitors of the clathrin-independent carriers/GPI-AP enriched early endosomal compartment (CLIC/GEEC) endocytic pathway, in a process independent of caveola formation. Caveolin-1 (CAV1) and CAV3 also inhibit the CLIC/GEEC pathway upon over-expression. Expression of caveolar protein leads to reduction in formation of early CLIC/GEEC carriers, as detected by quantitative electron microscopy analysis. Furthermore, the CLIC/GEEC pathway is upregulated in cells lacking CAV1/Cavin-1 or with reduced expression of Cavin-1 and Cavin-3. Inhibition by caveolins can be mimicked by the isolated caveolin scaffolding domain and is associated with perturbed diffusion of lipid microdomain components, as revealed by fluorescence recovery after photobleaching (FRAP) studies. In the absence of cavins (and caveolae) CAV1 is itself endocytosed preferentially through the CLIC/GEEC pathway, but the pathway loses polarization and sorting attributes with consequences for membrane dynamics and endocytic polarization in migrating cells and adult muscle tissue. We also found that noncaveolar Cavin-1 can act as a modulator for the activity of the key regulator of the CLIC/GEEC pathway, Cdc42. This work provides new insights into the regulation of noncaveolar clathrin-independent endocytosis by specific caveolar proteins, illustrating multiple levels of crosstalk between these pathways. We show for the first time a role for specific cavins in regulating the CLIC/GEEC pathway, provide a new tool to study this pathway, identify caveola-independent functions of the cavins and propose a novel mechanism for inhibition of the CLIC/GEEC pathway by caveolin.

Natasha Chaudhary, Guillermo A Gomez, Mark T Howes, Harriet P Lo, Kerrie-Ann McMahon, James A Rae, Nicole L. Schieber, Alpha S Yap, Robert G Parton - The University of Queensland, Institute for Molecular Bioscience, QLD Australia / Michelle M Hill - The University of Queensland, Diamantina Institute, QLD Australia / Katharina Gaus - University of New South Wales, Centre for Vascular Research and Australian Centre for NanoMedicine NSW Australia / Robert G Parton - Centre for Microscopy and Microanalysis, QLD Australia

  

 Journal of the American Chemical Society (JACS) (DOI: 10.1021/ja501745g)

A Robust and Versatile Photoinduced Living Polymerization of Conjugated and Unconjugated Monomers and Its Oxygen Tolerance

Jiangtao Xu, Kenward Jung, Amir Atme, Sivaprakash Shanmugam, Cyrille Boyer*

 

ja-2014-01745g 0011

Controlled/living radical polymerization techniques have transformed polymer chemistry in the last few decades, affording the production of polymers with precise control over both molecular weights and architectures. It is now possible to synthesize almost an infinite variety of macromolecules using nonspecialized equipment, finding applications in high-tech industry. However, they have several shortcomings. Until recently, living radical polymerizations could not be controlled by an external stimulus, such as visible light, pH, mechanical, chemical, etc. Moreover, they are usually sensitive to trace amounts of oxygen in the system. In this Article, we report a photoinduced living polymerization technique, which is able to polymerize a large range of monomers, including conjugated and unconjugated monomers, using ultralow concentrations of an iridium-based photoredox catalyst (typically 1 ppm to monomers) and a low energy visible LED as the light source (1–4.8 W, λmax = 435 nm). The synthesis of homopolymers with molecular weights ranging from 1000 to 2 000 000 g/mol was successfully achieved with narrow molecular weight distributions (Mw/Mn < 1.3). In addition, chain extensions of poly(methacrylate)s, poly(styrene), poly(N-vinyl pyrrolidinone), poly(vinyl ester)s, and poly(acrylate)s were performed to prepare diblock copolymers. The reusability of the catalyst was demonstrated by the synthesis of a decablock polymer by multiple chain extensions. Most importantly, this process was employed to prepare well-defined polymers and multiblock copolymers in the presence of air.

Centre for Advanced Macromolecular Design, School of Chemical Engineering, and Australian Centre for NanoMedicine, School of Chemical Engineering, UNSW Australia, Sydney NSW 2052 Australia

  

Book Chapter: Nanoscience (DOI: 10.1039/9781849737623-00225).

Chapter 8 Recent developments in the design of nanomaterials for photothermal and magnetic hyperthermia induced controllable drug delivery

Alexander E Dunn, Douglas J Dunn, May Lim, Cyrille Boyer, Nguyen Thi Kim Than

 Book cover: Nanoscience

Recent developments in anti-cancer drugs are focused on minimising side effects and improving treatment efficacy. This can be achieved by using a carrier that releases the drug in response to a stimulus. In recent years, research has been directed towards the use of light or alternating magnetic fields as remote stimuli in what is called photothermal and magnetic hyperthermia induced controllable drug delivery, respectively. Much progress has also been made in the use of nanoparticles and polymeric macromolecules as drug carriers. By combining polymers with inorganic nanoparticles into a single entity, it becomes possible to harness the light or magnetic field responsive properties of nanoparticles with the drug storage and release properties of polymers for drug delivery. In this review, we explore recent developments of polymer-nanoparticle hybrids drug carriers for photothermal and magnetic hyperthermia controllable drug delivery.

Australian Centre for NanoMedicine, University of New South Wales, Sydney NSW 2052 Australia

 
 

Journal of Materials Chemistry B (DOI 10.1039/C4TB0028iD)

Chemical patterning on preformed porous silicon photonic crystals: towards multiplex detection of protease activity at precise positions

Ying Zhu,a   Alexander H Soeriyadi,a   Stephen G Parker,a   Peter J Reeceb, J Justin Gooding*a

 Graphical abstract: Chemical patterning on preformed porous silicon photonic crystals: towards multiplex detection of protease activity at precise positions

Porous silicon (PSi) rugate filters modified with alkyne-terminated monolayers were chemically patterned using a combination of photolithography of photoresist and click chemistry. Two chemical functionalities were obtained by conjugating, via click reactions, ethylene glycol moieties containing two different terminal groups to discrete areas towards the exterior of a PSi rugate filter. The patterning of biological species to the functionalized surface was demonstrated through the conjugation of fluorescein isothiocyanate labelled bovine serum albumin (FITC-BSA). Fluorescence microscopy showed selective positioning of FITC-BSA at discretely functionalized areas. Meanwhile, the optical information from precisely defined positions on the patterned surface was monitored by optical reflectivity measurements. The optical measurements revealed successful step-wise chemical functionalization followed by immobilization of gelatin. Multiplex detection of protease activity from different array elements on the patterned surface was demonstrated by monitoring the blue shifts in the reflectivity spectra resulted from the digestion of gelatin by subtilisin. Precise information from both individual elements and average population was acquired. This technique is important for the development of PSi into a microarray platform for highly parallel biosensing applications, especially for cell-based assays.

aSchool of Chemistry and the Australian Centre for NanoMedicine, University of New South Wales, Sydney 2052 Australia. bSchool of Physics, University of New South Wales, Sydney 2052 Australia

  

British Journal of Pharma (DOI: 10.1111/bph.12704).

Movers and shakers: cell cytoskeleton in cancer metastasis

C M Fife1,2, J A McCarroll1,2, M Kavallaris1,2,*

 Cover image for Vol. 171 Issue 18

Metastasis is responsible for the greatest number of cancer deaths. Metastatic disease, or the movement of cancer cells from one site to another, is a complex process requiring dramatic remodeling of the cell cytoskeleton. The various components of the cytoskeleton, actin (microfilaments), microtubules and intermediate filaments, are highly integrated and their functions are well orchestrated in normal cells. In contrast, mutations and abnormal expression of cytoskeletal and cytoskeletal-associated proteins play an important role in the ability of cancer cells to resist chemotherapy and metastasise. Studies on the role of actin and its interacting partners has highlighted key signalling pathways, such as the Rho GTPases, and downstream effector proteins that, through the cytoskeleton, mediate tumour cell migration, invasion and metastasis. An emerging role for microtubules in tumour cell metastasis is being unraveled and there is increasing interest in the cross-talk between key microtubule interacting proteins and the actin cytoskeleton, which may provide novel treatment avenues for metastatic disease. Improved understanding of how the cytoskeleton, and its interacting partners, influence tumour cell migration and metastasis is leading to the development of novel therapeutics against aggressive and metastatic disease.

1Tumour Biology and Targeting Program Children's Cancer Institute Australia, Lowy Cancer Research Centre UNSW Australia Rankwick NSW Australia 2031 2Australian Centre for NanoMedicine UNSW Australia Sydney NSW Australia

  

Histochemistry and Cell Biology (DOI 10.1007/s00418-014-1208-z)

Method for co-cluster analysis in multichannel single-molecule localisation data

Jérémie Rossy1, Edward Cohen2, Katharina Gaus1, Dylan M Owen3

 Histochemistry and Cell Biology

We demonstrate a combined univariate and bivariate Getis and Franklin’s local point pattern analysis method to investigate the co-clustering of membrane proteins in two-dimensional single-molecule localisation data. This method assesses the degree of clustering of each molecule relative to its own species and relative to a second species. Using simulated data, we show that this approach can quantify the degree of cluster overlap in multichannel point patterns. The method is validated using photo-activated localisation microscopy and direct stochastic optical reconstruction microscopy data of the proteins Lck and CD45 at the T cell immunological synapse. Analysing co-clustering in this manner is generalizable to higher numbers of fluorescent species and to three-dimensional or live cell data sets.

1Centre for Vascular Research and Australian Centre for NanoMedicine, University of New South Wales, Sydney Australia 2Department of Mathematics, Imperial College London, London UK 3Department of Physics and Randall Division of Cell and Molecular Biophysics, King’s College London London UK

  

Polymer Chemistry (DOI: 10.1039/C4PY00150H)

Spatial and temporal control of drug release through pH and alternating magnetic field induced breakage of Schiff base bond

Alexander E Dunn,ab Douglas J Dunn,ab Alexander Macmillan,c Renee Whan,c Tim Stait-Gardner,d William S Price,d May Lim*a, Cyrille Boyer*b

 polymerchemistry2014

P(DEGMA-co-OEGMA-b-[TMSPMA-co-VBA])@silica@magnetite polymer–nanoparticle composites have been developed as a platform for controllable drug release. The nanocomposite facilitates controllable release of therapeutic molecules through breakage of pH and heat labile Schiff base bonds that bind the molecules to the polymer. This enables dual-stimuli responsive drug release in response to the acidic microenvironment of cancerous cells and heat generated by the magnetite nanoparticles when subjected to an alternating magnetic field, thereby permitting spatial and temporal control over ‘burst’ release of the drugs. The nanocomposite has also been shown to be effective at improving magnetic resonance imaging contrast through enhancement of spin–spin relaxivity.

aARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052 Australia bAustralian Centre for NanoMedicine and Centre for Advanced Macromolecular Design, School of Chemical Engineering, University of New South Wales, Sydney NSW 2052 Australia cBiomedical Imaging Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney NSW 2052 Australia dNanoscale Organisation and Dynamics Group, School of Science and Health, University of Western Sydney, Penrith NSW 2751 Australia

  

Biomicromolecules (DOI: 10.1021/bm401526d)

Dextran-Based Doxorubicin Nanocarriers with Improved Tumor Penetration

Sharon M Sagnella, Hien Duong, Alex MacMillan§, Cyrille Boyer, Renee Whan§, Joshua A McCarroll, Thomas P Davis, Maria Kavallaris*

 bm-2013-01526d 0011

Drug delivery systems with improved tumor penetration are valuable assets as anticancer agents. A dextran-based nanocarrier system with aldehyde functionalities capable of forming an acid labile linkage with the chemotherapy drug doxorubicin was developed. Aldehyde dextran nanocarriers (ald-dex-dox) demonstrated efficacy as delivery vehicles with an IC50 of ∼300 nM against two-dimensional (2D) SK-N-BE(2) monolayers. Confocal imaging showed that the ald-dex-dox nanocarriers were rapidly internalized by SK-N-BE(2) cells. Fluorescence lifetime imaging microscopy (FLIM) analysis indicated that ald-dex-dox particles were internalized as intact complexes with the majority of the doxorubicin released from the particle four hours post uptake. Accumulation of the ald-dex-dox particles was significantly enhanced by ∼30% in the absence of glucose indicating a role for glucose and its receptors in their endocytosis. However, inhibition of clathrin dependent and independent endocytosis and macropinocytosis as well as membrane cholesterol depletion had no effect on ald-dex-dox particle accumulation. In three-dimensional (3D) SK-N-BE(2) tumor spheroids, which more closely resemble a solid tumor, the ald-dex-dox nanoparticles showed a significant improvement in efficacy over free doxorubicin, as evidenced by decreased spheroid outgrowth. Drug penetration studies in 3D demonstrated the ability of the ald-dex-dox nanocarriers to fully penetrate into a SK-N-BE(2) tumor spheroids, while doxorubicin only penetrates to a maximum distance of 50 μM. The ald-dex-dox nanocarriers represent a promising therapeutic delivery system for the treatment of solid tumors due to their unique enhanced penetration ability combined with their improved efficacy over the parent drug in 3D.

Australian Centre for Nanomedicine and  §Biomedical Imaging Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia Children’s Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, PO Box 81 Randwick Australia; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Melbourne, Victoria Australia; Department of Chemistry, University of Warwick, Coventry United Kingdom
  

Polymer Chemistry (DOI:L 10.10396/C3PY01638B).

Optimising the enzyme response of a porous silicon photonic crystal via the modular design of enzyme sensitive polymers

Alexander H Soeriyadi,ab   Bakul Gupta,ab   Peter J Reecec, J Justin Gooding*ab

 polymerchemistryfeb2014diagram

We describe the immobilization within the pores of a porous silicon photonic crystal of an enzyme degradable polymer network, for optical biosensing. A porous silicon (PSi) rugate filter is a one-dimensional photonic crystal with a high-reflectivity optical resonance that is sensitive to small changes in the refractive index of the pore space permeating through the structure. An enzymatically degradable polymer network was constructed by first “clicking” an antifouling copolymer, poly(oligo ethylene glycol-co-acrylic acid)-N3, to an alkyne functionalized PSi surface via copper(I)-catalysed alkyne–azide cycloaddition (CuAAC) reaction. MMP-2 or MMP-9 specific cleavable peptide sequences, with diamine functional groups, were then added, using a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS) chemistry to react with the acrylic acid group. The polymer network was completed by further attachment of a sacrificial polymer, poly(hydroxyethyl acrylate-co-N-hydroxysuccinimide ester acrylate). X-ray photoelectron spectroscopy (XPS) and optical reflectivity measurements reveal successful modification of the PSi with the polymer–peptide network. Exposure of the biosensor platform to solutions of matrix metalloproteinases, MMP-2 or MMP-9, caused a change in the average refractive index of the photonic crystal, resulting in a discernible blue shift in the reflectivity spectra. The blue shift indicated the degradation of the polymer network within the porous network. Selective detection of different MMPs was demonstrated, via the use of different peptide sequences, which are selectively digestible by different MMPs, to link the two polymers.

aSchool of Chemistry, University of New South Wales, Sydney NSW 2052 Australia bAustralian Centre of NanoMedicine, University of New South Wales, Sydney NSW  2052 Australia cSchool of Physics, University of New South Wales, Sydney NSW 2052 Australia

  

 Polymer Chemistry (DOI: 10.1039/C39C3PYO1778H)

A block copolymer-stabilized co-precipitation approach to magnetic iron oxide nanoparticles for potential use as MRI contrast agents

Johan S Basuki, ‡a Alexandre Jacquemin,‡b Lars Esser,ac Yang Li,ab Cyrille Boyer*ab, Thomas P Davis*cd

 diagrampolymerchemistryfeb2014

A library of magnetic nanoparticles was generated using in situ co-precipitation of ferrous (Fe2+) and ferric(Fe3+) ions from aqueous solutions in the presence of functional block copolymers. Three different iron oxide anchoring groups, viz. , phosphonic acid, carboxylic acid or glycerol were incorporated into well-defined diblock copolymers of poly(oligoethylene glycol acrylate) employed to stabilize the iron oxide nanoparticles. The [copolymer] : [Fe] ratio was varied to wield control over nanoparticle diameters within the range of 7–20 nm. The relationship between colloidal stability and nanoparticle crystallinity was investigated using dynamic light scattering, transmission electron microscopy and X-ray diffraction measurements. The amount of polymer employed during the co-precipitation proved critical in governing crystallinity and colloidal stability. We report a correlation between the polymer grafting density and the chemical structure of the anchoring group. Finally, the transverse relaxivity of the iron oxide nanoparticles in water, was investigated using a 9.4T magnetic resonance imaging scanner yielding values varying from 70 to 370 mM

aAustralian Centre for NanoMedicine, School of Chemical Engineering, University of New South Wales, 2052 Sydney Australia bCentre for Advanced Macromolecular Design, School of Chemical Engineering, University of New South Wales 2052 Sydney Australia. cMonash Institute of Pharmaceutical Sciences, Monash University Parkville VIC 3052 Australia dDepartment of Chemistry, University of Warwick, ULCV4 7AL Coventry UK

 

  

Optical Express (doi.org/10.1364/OE.22.002973)

Fluorescence spectral correlation spectroscopy (FSCS) for probes with highly overlapping emission spectra

 opticsexpress

We present a fluorescence correlation spectroscopy (FCS) approach to obtain spectral cross-talk free auto- and cross-correlation functions for probes with highly overlapping emission spectra. Confocal microscopes with either a hyperspectral EM-CCD or six-channel PMT array spectral detection were used, followed by a photon filtering correlation approach that results in spectral unmixing. The method is highly sensitive and can distinguish between Atto488 and Oregon Green 488 signals so that auto-correlation curves can be fitted without the need for cross-talk correction. We also applied the approach to the membrane dye Laurdan whose emission is dependent on the lipid order within the bilayer. With fluorescence spectral correlation spectroscopy (FSCS), we could obtain spectral cross-talk free auto- and cross-correlation functions corresponding to Laurdan located in liquid ordered and liquid disordered phases.

 

Frontiers in Physiology (DOI 10.3389/fphys.2014.00002)

Potential applications of nanotechnology for the diagnosis and treatment of pancreatic cancer

McCarroll J1, Teo J2, Boyer C3, Goldstein D4, Kavallaris M1, Phillips PA5

 

Figure 1

Despite improvements in our understanding of pancreatic cancer and the emerging concept of personalized medicine for the treatment of this disease, it is still the fourth most common cause of cancer death in the western world. It is established that pancreatic cancer is a highly heterogeneous disease with a complex tumor microenvironment. Indeed the extensive stroma surrounding the cancer cells has been shown to be important in promoting tumor growth and metastases, as well as sequestering chemotherapeutic agents consequently decreasing delivery to the tumor cells. Nanotechnology has come to the forefront in the areas of medical diagnostics, imaging, and therapeutic drug delivery. This review will focus on the potential applications of nanotechnology for diagnosis, imaging, and delivery of therapeutic agents for the treatment of pancreatic cancer.

1Tumor Biology and Targeting Program, Lowy Cancer Research Centre, Children's Cancer Institute Australia, University of New South Wales, Sydney NSW Australia 2Australian Centre for NanoMedicine, University of New South Wales, Sydney NSW Australia 3Panceatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney NSW Australia

  

Chemphyschem. (doi: 10.1002/cphc.201301041)

Insights into adhesion biology using single-molecule localization microscopy

Tabarin T, Pageon SV, Bach CT, Lu Y, O'Neill GM, Gooding JJ, Gaus K

 chemphyschemcoverfeb2014

Focal adhesions are complex multi-protein structures that mediate cell adhesion and cell migration in multicellular organisms. Most of the protein components involved in focal adhesion formation have been identified, but a major challenge remains: determination of the spatial and temporal dynamics of adhesion proteins in order to understand the molecular mechanisms of adhesion assembly, maturation, signal regulation, and disassembly. Progress in this field has been hampered by the limited resolution of fluorescence microscopy. Recent advances have led to the development of super-resolution techniques including single-molecule localization microscopy (SMLM). Here, we discuss how the application of these techniques has revealed important new insights into focal adhesion structure and dynamics, including the first description of the three-dimensional nano-architecture of focal adhesions and of the dynamic exchange of integrins in focal adhesions. Hence, SMLM has contributed to the refinement of existing models of adhesions as well as the establishment of novel models, thereby opening new research directions. With current improvements in SMLM instrumentation and analysis, it has become possible to study cellular adhesions at the single-molecule level.

[a]T Tabarin, S V Pageon, C T T Bach, K Gaus Centre for Vascular Research University of New South Wales Sydney 2052 Australia [b]Y Lu, J J Gooding School of Chemistry University of New South Wales Sydney 2052 Australia [c]Y Lu, J J Gooding, K Gaus Australian Centre for NanoMedicine University of New South Wales Sydney 2052 Australia [d]G M O’Neill Children’s Cancer Research Unit Kids Research Institute The Children’s Hospital at Westmead Westmead 2145 Australia

  

Polymer Chemistry (DOI: 10.1039/C4PY90005G)

Themed issue: synthesis of polymeric nanomaterials for medicine

Cyrille Boyerab, Thomas P Daviscd

 coverpolymerchemistryjan2014

The application of polymeric nano-materials for medical applications has become a growing field of research. Using recent advances in macromolecular engineering tools, such as controlled/living polymerization and click chemistry, polymer chemists now have the ability to control the sequence, functionality and microstructures of synthetic polymers, offering the  construction of more complex macromolecules with the objective of mimicking natural polymers. These well-defined synthetic polymers have found applications in nanotechnology, biotechnology and material science, and it is expected that the importance of synthetic polymers will continue to grow in medical and pharmaceutical applications, especially in the preparation of smart polymeric nano-objects. For example, polymeric nano-particles can be employed for the transport and delivery of therapeutic compounds which have poor solubility in biological fluid. Such polymers and nanoparticles will allow for the treatment and restoration of normal functions in cellular and biological systems.

aAustralian Centre for NanoMedicine, University of New South Wales, Sydney Australia bCentre for Advanced Macromolecular Design, School of Chemical Engineering, University of New South Wales, Sydney Australia CMonash Institute of Pharmaceutical Sciences, Monash University, Parkville Melbourne 3052 Australia dSchool of Chemistry, University of Warwick UK

  

Journal of Physical Chemistry C (DOI: 10.1021/jp411979x)

Electrochemical and Theoretical Study of π–π Stacking Interactions between Graphitic Surfaces and Pyrene Derivatives

Abstract Image 

In this study, the reversibility of π–π stacking interactions at graphite electrodes (GE) of pyrene, 1-aminopyrene, 1-pyrenecarboxylic acid, and doxorubicin hydrochloride (DOX) have been studied. The adsorption and desorption of these π-orbital-rich molecules was characterized using X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV). The experimental investigations were complemented with a density functional theory study of the interaction between these π-orbital-rich molecules and graphite. It was demonstrated that the charged pyrene derivatives could be electrochemically desorbed from the graphitic surfaces, when a sufficiently high potential of the same charge as the pyrene derivative, was applied to the electrode. The duration of the applied potential, the pH and the magnitude of the applied potential during potential pulsing were found to be important with regards to the desorption efficiency. Up to 90% of charged pyrene derivatives could be removed from the electrode surface within 60 s via potential pulsing. However, these parameters produced insignificant effects on neutral pyrene bound to the graphite. A potential application of this electrochemically induced desorption of π-rich species in drug delivery was demonstrated via the release of adsorbed doxorubicin (DOX).

College of Chemistry, Chemical and Environmental Engineering, Qingdao University, Qingdao 266071 China Laboratory of Fiber Materials and Modern Textile, the Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071 China §School of Chemistry and the Australian Centre for NanoMedicine, The University of New South Wales, Sydney New South Wales 2052 Australia
  

Journal of Drug Targeting (doi:10.3109/1061186X.2013.878941)

Magnetic catechin–dextran conjugate as targeted therapeutic for pancreatic tumour cells

 journal of drug targeting

Background: Catechin–dextran conjugates have recently attracted a lot of attention due to their anticancer activity against a range of cancer cells. Magnetic nanoparticles have the ability to concentrate therapeutically important drugs due to their magnetic-spatial control and provide opportunities for targeted drug delivery. Purpose: Enhancement of the anticancer efficiency of catechin–dextran conjugate by functionalisation with magnetic iron oxide nanoparticles. Methods: Modification of the coating shell of commercial magnetic nanoparticles (Endorem) composed of dextran with the catechin–dextran conjugate. Results: Catechin–dextran conjugated with Endorem (Endo–Cat) increased the intracellular concentration of the drug and it induced apoptosis in 98% of pancreatic tumour cells placed under magnetic field. Discussion: The conjugation of catechin–dextran with Endorem enhances the anticancer activity of this drug and provides a new strategy for targeted drug delivery on tumour cells driven by magnetic field. Conclusion: The ability to spatially control the delivery of the catechin–dextran by magnetic field makes it a promising agent for further application in cancer therapy.

1Children's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, NSW Australia 2Australian Centre for NanoMedicine, University of New South Wales, NSW Australia 3NEST Scuola Normale Superiore and Istituto Nanoscienze-CNR Piazza San Silvestro Pisa Italy 4Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Pisa Italy 5Saha Institute of Nuclear Physics, Kolkata India 6Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS) Italy 7Leibniz Institute for Solid State and Materials Research Dresden, Dresden Germany

  

Chemical Society Review DOI: 10.1039/C3CS60353A

Colloidal silicon quantum dots: from preparation to the modification of self-assembled monolayers (SAMs) for bio-applications

Xiaoyu Cheng,ab, Stuart B Lowe,ab Peter J Reece,c J Justin Gooding*ab

 chemsocietyreviewjan2014

Concerns over possible toxicities of conventional metal-containing quantum dots have inspired growing research interests in colloidal silicon nanocrystals (SiNCs), or silicon quantum dots (SiQDs). This is related to their potential applications in a number of fields such as solar cells, optoelectronic devices and fluorescent bio-labelling agents. The past decade has seen significant progress in the understanding of fundamental physics and surface properties of silicon nanocrystals. Such understanding is based on the advances in the preparation and characterization of surface passivated colloidal silicon nanocrystals. In this critical review, we summarize recent advances in the methods of preparing high quality silicon nanocrystals and strategies for forming self-assembled monolayers (SAMs), with a focus on their bio-applications. We highlight some of the major challenges that remain, as well as lessons learnt when working with silicon nanocrystals (239 references).

aSchool of Chemistry, University of New South Wales, Sydney NSW 2052 Australia bAustralian Centre for Nanomedicine, University of New South Wales, Sydney NSW 2052 Australia cSchool of Physics, University of New South Wales, Sydney NSW 2052 Australia

  

ChemElectroChem (DOI: 10.1002/celc.201300136)

The Effect of Interfacial Design on the Electrochemical Detection of DNA and MicroRNA Using Methylene Blue at Low-Density DNA Films

Roya Tavallaie1,2,Nadim Darwish1, Magdalena Gebala3,4, D Brynn Hibbert1, J Justin Gooding1,2

 ChemElectroChem

Herein, we study the effect of interfacial design, specifically the orientation of a DNA probe strand, the length of the diluent and the type of target (DNA vs. microRNA), on the electrochemical response from methylene blue (MB) at low-density DNA films. The probe DNA interfaces are formed from mixed self-assembled monolayers of single-stranded DNA (ss-DNA) and a hydroxyl terminated alkanethiol diluents on gold surfaces. Variation in the current from the DNA–MB complex after hybridization with complementary and single adenine–cytosine mismatch DNA target is shown to depend on whether the 3′ or 5′ end is tethered to the electrode and the length of the diluent (6-mercapto-1-hexanol vs. 9-mercapto-1-nonanol). The sensors show better mismatch discrimination of single base pairs when both the duplexes are tethered from the 5′ end to the electrode and with a longer-chain (9-mercapto-1-nonanol) diluent. Of particular note is our demonstration that the DNA/microRNA duplex exhibits greater single adenine–cytosine mismatch discrimination when compared to the corresponding DNA/DNA duplex. This study contributes to the development of selective DNA and microRNA biosensors.

[a]R Tavallaie, N Darwish, D B Hibbert, J J Gooding School of Chemistry University of New South Wales Sydney NSW 2052 Australia [b]R Tavallaie,  J J Gooding Australian Centre for NanoMedicine University of New South Wales Sydney NSW 2052 Australia [c]M Gebala Analytische Chemie—Elektroanalytik & Sensorik Ruhr-Universitat Bochum Universitatsstr.150 44780 Bochum Germany [d]M Gebala Department of Biochemistry Stanford School of Medicine, Beckman Center, B46 279 W Campus Drive MC 5307 Stanford CA 94305 (USA)