ORCID Profile
0000-0003-1547-2855
Current Organisation
University of Queensland
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Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Elsevier BV
Date: 02-2019
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7CC04291D
Abstract: Zinc-coordination and C-peptide complexation stabilize IAPP and inhibit its amyloid aggregation.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2013
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9NR02407G
Abstract: Featuring small sizes, caged structures, low cytotoxicity and the capability to cross biological barriers, fullerene hydroxy derivatives named fullerenols have been explored as nanomedicinal candidates for amyloid inhibition.
Publisher: Springer Science and Business Media LLC
Date: 14-01-2016
DOI: 10.1038/SREP19463
Abstract: Experimental studies have shown that many naturally occurring polyphenols have inhibitory effect on the aggregation of several proteins. Here, we use discrete molecular dynamics (DMD) simulations and high-throughput dynamic light scattering (DLS) experiments to study the anti-aggregation effects of two polyphenols, curcumin and resveratrol, on the aggregation of islet amyloid polypeptide (IAPP or amylin). Our DMD simulations suggest that the aggregation inhibition is caused by stabilization of small molecular weight IAPP off-pathway oligomers by the polyphenols. Our analysis indicates that IAPP-polyphenol hydrogen bonds and π-π stacking combined with hydrophobic interactions are responsible for the stabilization of oligomers. The presence of small oligomers is confirmed with DLS measurements in which nanometer-sized oligomers are found to be stable for up to 7.5 hours, the time frame within which IAPP aggregates in the absence of polyphenols. Our study offers a general anti-aggregation mechanism for polyphenols and further provides a computational framework for the future design of anti-amyloid aggregation therapeutics.
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Wiley
Date: 11-06-2019
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.JHAZMAT.2012.05.095
Abstract: The combined chemical and ecotoxicological characterization of oil shale combustion fly ash was performed. Ash was s led from the most distant point of the ash-separation systems of the Balti and Eesti Thermal Power Plants in North-Eastern Estonia. The fly ash proved potentially hazardous for tested aquatic organisms and high alkalinity of the leachates (pH>10) is apparently the key factor determining its toxicity. The leachates were not genotoxic in the Ames assay. Also, the analysis showed that despite long-term intensive oil-shale combustion accompanied by considerable fly ash emissions has not led to significant soil contamination by hazardous trace elements in North-Eastern Estonia. Comparative study of the fly ash originating from the 'new' circulating fluidized bed (CFB) combustion technology and the 'old' pulverized-fired (PF) one showed that CFB fly ash was less toxic than PF fly ash. Thus, complete transfer to the 'new' technology will reduce (i) atmospheric emission of hazardous trace elements and (ii) fly ash toxicity to aquatic organisms as compared with the 'old' technology.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7BM01012E
Abstract: Phosphoryl choline grafting secured high cellular uptake and increased transcytosis of superparamagnetic iron oxide nanoparticles through a model blood brain barrier.
Publisher: Research Square Platform LLC
Date: 19-01-2022
DOI: 10.21203/RS.3.RS-1161788/V1
Abstract: Alzheimer’s disease (AD) is a major cause of dementia debilitating the global ageing population. Current understanding of the AD pathophysiology implicates the aggregation of amyloid beta (Aβ) as causative to neurodegeneration, with tauopathies and neuroinflammation considered as other major culprits. Curiously, vascular endothelial barrier dysfunction is strongly associated with Aβ deposition and 80-90% AD subjects also experience cerebral amyloid angiopathy. Here we show amyloid proteins-induced endothelial leakiness (APEL) in human microvascular endothelial monolayers as well as in mouse cerebral vasculature. Using signaling pathway assays and discrete molecular dynamics, we revealed that the angiopathy first arose from a disruption to vascular endothelial (VE)-cadherin junctions exposed to the nanoparticulates of Aβ oligomers and seeds, preceding the earlier implicated proinflammatory and pro-oxidative stressors to endothelial leakiness. These findings are analogous to nanomaterials-induced endothelial leakiness (NanoEL), a major phenomenon in nanomedicine depicting the paracellular transport of anionic inorganic nanoparticles in the vasculature. As APEL also occurred with the anionic seeds of pathogenic alpha synuclein and functional FapC bacterial amyloid, this study projects a general new paradigm for elucidating the vascular permeation, systemic spread, and cross-seeding of amyloid proteins that underlie the pathogeneses of AD, Parkinson’s, as well as a range of amyloid diseases.
Publisher: Wiley
Date: 07-08-2017
Abstract: Polyethylene glycol (PEG) is widely used as an antifouling and stealth polymer in surface engineering and nanomedicine. However, recent research has revealed adverse effects of bioaccumulation and immunogenicity following the administration of PEG, prompting this proteomic examination of the plasma protein coronae association with superparamagnetic iron oxide nanoparticles (IONPs) grafted with brushed PEG (bPEG) and an alternative, brushed phosphorylcholine (bPC). Using label-free quantitation by liquid chromatography tandem-mass spectrometry, this study determines protein abundances for the in vitro hard coronae of bare, bPC-, and bPEG-grafted IONPs in human plasma. This study also shows unique protein compositions in the plasma coronae of each IONP, including enrichment of coagulation factors and immunogenic complement proteins with bPEG, and enhanced binding of apolipoproteins with bPC. Functional analysis reveals that plasma protein coronae elevate the horseradish peroxidase-like activities of the bPC- and bPEG-IONPs by approximately twofold, an effect likely mediated by the erse composition and physicochemical properties of the polymers as well as their associated plasma proteins. Taken together, these observations support the rational design of stealth polymers based on a quantitative understanding of the interplay between IONPs and the plasma proteome, and should prove beneficial for the development of materials for nanomedicine, biosensing, and catalysis.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.BBAMEM.2018.01.015
Abstract: Protein aggregation is a ubiquitous phenomenon underpinning the origins of a range of human diseases. The amyloid aggregation of human islet amyloid polypeptide (IAPP) and alpha synuclein (αS), specifically, is a hallmark of type 2 diabetes (T2D) and Parkinson's disease impacting millions of people worldwide. Although IAPP and αS are strongly associated with pancreatic β-cell islets and presynaptic terminals, they have also been found in blood circulation and the gut. While extensive biophysical and biochemical studies have been focused on IAPP and αS interacting with cell membranes or model lipid vesicles, the roles of plasma proteins on the amyloidosis and membrane association of these two major types of amyloid proteins have rarely been examined. Using a thioflavin T kinetic assay, transmission electron microscopy and a hemolysis assay here we show that human serum albumin, the most abundant protein in the plasma, impeded the fibrillization and mitigated membrane damage of both IAPP and αS. This study offers a new insight on the native inhibition of amyloidosis.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2012
DOI: 10.1007/S11356-012-1290-5
Abstract: Although silver nanoparticles (NPs) are increasingly used in various consumer products and produced in industrial scale, information on harmful effects of nanosilver to environmentally relevant organisms is still scarce. This paper studies the adverse effects of silver NPs to two aquatic crustaceans, Daphnia magna and Thamnocephalus platyurus. For that, silver NPs were synthesized where Ag is covalently attached to poly(vinylpyrrolidone) (PVP). In parallel, the toxicity of collargol (protein-coated nanosilver) and AgNO₃ was analyzed. Both types of silver NPs were highly toxic to both crustaceans: the EC50 values in artificial freshwater were 15-17 ppb for D. magna and 20-27 ppb for T. platyurus. The natural water (five different waters with dissolved organic carbon from 5 to 35 mg C/L were studied) mitigated the toxic effect of studied silver compounds up to 8-fold compared with artificial freshwater. The toxicity of silver NPs in all test media was up to 10-fold lower than that of soluble silver salt, AgNO₃. The pattern of the toxic response of both crustacean species to the silver compounds was almost similar in artificial freshwater and in natural waters. The chronic 21-day toxicity of silver NPs to D. magna in natural water was at the part-per-billion level, and adult mortality was more sensitive toxicity test endpoint than the reproduction (the number of offspring per adult).
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6EN00579A
Abstract: We believe continued development of the field of environmental health and safety of nanomaterials (nanoEHS) hinges on a critical extension from reporting macroscopic and microscopic phenomena to understanding nano-biomolecular interactions.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8NR07180B
Abstract: Graphene quantum dots are biocompatible zero-dimensional nanostructures, which displayed a potency in rescuing zebrafish embryos from the toxicity of human islet amyloid polypeptide.
Publisher: Springer Science and Business Media LLC
Date: 07-2018
Publisher: Elsevier BV
Date: 08-2013
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7CP06670H
Abstract: Micellar lysophosphatidylcholine inhibits the aggregation of human islet amyloid polypeptide (IAPP).
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5PY02024G
Abstract: A new and facile strategy for grafting IONPs by phosphonic acic terminated PC brushes has been demonstrated and characterized in vitro .
Publisher: Public Library of Science (PLoS)
Date: 2013
Publisher: Public Library of Science (PLoS)
Date: 21-07-2014
Publisher: Springer Science and Business Media LLC
Date: 24-07-2013
DOI: 10.1038/SREP02273
Publisher: American Chemical Society (ACS)
Date: 08-08-2018
DOI: 10.1021/ACS.NANOLETT.8B02446
Abstract: Amyloid diseases are global epidemics with no cure available. Herein, we report a first demonstration of in vivo mitigation of amyloidogenesis using biomimetic nanotechnology. Specifically, the amyloid fragments (b
Publisher: American Chemical Society (ACS)
Date: 21-01-2019
Abstract: The use of nanomaterials has recently become an emerging strategy against protein amyloidosis associated with a range of metabolic and brain diseases. To facilitate research in this area, here we first demonstrated the use of hyperspectral imaging (HSI) and COMSOL simulations for reporting the aggregation of human islet amyloid polypeptides (IAPPs), a hallmark of type 2 diabetes, as well as the physical interactions between the peptide and gold nanoparticles (AuNPs) grafted with citrate and poly(ethylene glycol) (PEG
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.ENVINT.2015.10.014
Abstract: Within the FP7 EU project NanoValid a consortium of six partners jointly investigated the hazard of silver nanoparticles (AgNPs) paying special attention to methodical aspects that are important for providing high-quality ecotoxicity data. Laboratories were supplied with the same original stock dispersion of AgNPs. All partners applied a harmonised procedure for storage and preparation of toxicity test suspensions. Altogether ten different toxicity assays with a range of environmentally relevant test species from different trophic levels were conducted in parallel to AgNP characterisation in the respective test media. The paper presents a comprehensive dataset of toxicity values and AgNP characteristics like hydrodynamic sizes of AgNP agglomerates and the share (%) of Ag(+)-species (the concentration of Ag(+)-species in relation to the total measured concentration of Ag). The studied AgNP preparation (20.4±6.8 nm primary size, mean total Ag concentration 41.14 mg/L, 46-68% of soluble Ag(+)-species in stock, 123.8±12.2 nm mean z-average value in dH2O) showed extreme toxicity to crustaceans Daphnia magna, algae Pseudokirchneriella subcapitata and zebrafish Danio rerio embryos (EC50<0.01 mg total Ag/L), was very toxic in the in vitro assay with rainbow trout Oncorhynchus mykiss gut cells (EC50: 0.01-1 mg total Ag/L) toxic to bacteria Vibrio fischeri, protozoa Tetrahymena thermophila (EC50: 1-10 mg total Ag/L) and harmful to marine crustaceans Artemia franciscana (EC50: 10-100 mg total Ag/L). Along with AgNPs, also the toxicity of AgNO3 was analyzed. The toxicity data revealed the same hazard ranking for AgNPs and AgNO3 (i.e. the EC50 values were in the same order of magnitude) proving the importance of soluble Ag(+)-species analysis for predicting the hazard of AgNPs. The study clearly points to the need for harmonised procedures for the characterisation of NMs. Harmonised procedures should consider: (i) measuring the AgNP properties like hydrodynamic size and metal ions species in each toxicity test medium at a range of concentrations, and (ii) including soluble metal salt control both in toxicity testing as well as in Ag(+)-species measurements. The present study is among the first nanomaterial interlaboratory comparison studies with the aim to improve the hazard identification testing protocols.
Publisher: American Chemical Society (ACS)
Date: 10-05-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0NH00548G
Abstract: Impactful research in nanomedicine depends upon the adequate use of cellular and animal models. Here we systematically review and evaluate the in vitro and in vivo models which have enabled the development of anti-amyloidosis nanomedicines.
Publisher: Pleiades Publishing Ltd
Date: 2014
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB01634H
Abstract: The protein corona is a concept central to a range of disciplines exploiting the bio–nano interface.
Publisher: American Chemical Society (ACS)
Date: 24-12-2020
Publisher: IOP Publishing
Date: 30-07-2013
DOI: 10.1088/0957-4484/24/34/345101
Abstract: We report on the dose-dependent inhibition of firefly luciferase activity induced by exposure of the enzyme to 20 nm citrate-coated silver nanoparticles (AgNPs). The inhibition mechanism was examined by characterizing the physicochemical properties and biophysical interactions of the enzyme and the AgNPs. Consistently, binding of the enzyme induced an increase in zeta potential from -22 to 6 mV for the AgNPs, triggered a red-shift of 44 nm in the absorbance peak of the AgNPs, and rendered a 'protein corona' of 20 nm in thickness on the nanoparticle surfaces. However, the secondary structures of the enzyme were only marginally affected upon formation of the protein corona, as verified by circular dichroism spectroscopy measurement and multiscale discrete molecular dynamics simulations. Rather, inductively coupled plasma mass spectrometry measurement revealed a significant ion release from the AgNPs. The released silver ions could readily react with the cysteine residues and N-groups of the enzyme to alter the physicochemical environment of their neighboring catalytic site and subsequently impair the enzymatic activity.
Publisher: American Chemical Society (ACS)
Date: 31-10-2017
Publisher: Elsevier BV
Date: 10-2015
Publisher: Bentham Science Publishers Ltd.
Date: 16-06-2015
DOI: 10.2174/1568026615666150506150109
Abstract: The knowledge on potential harmful effects of metallic nanomaterials lags behind their increased use in consumer products and therefore, the safety data on various nanomaterials applicable for risk assessment are urgently needed. In this study, 11 metal oxide nanoparticles (MeOx NPs) prepared using flame pyrolysis method were analyzed for their toxicity against human alveolar epithelial cells A549, human epithelial colorectal cells Caco2 and murine fibroblast cell line Balb/c 3T3. The cell lines were exposed for 24 h to suspensions of 3-100 μg/mL MeOx NPs and cellular viability was evaluated using. Neutral Red Uptake (NRU) assay. In parallel to NPs, toxicity of soluble salts of respective metals was analyzed, to reveal the possible cellular effects of metal ions shedding from the NPs. The potency of MeOx to produce reactive oxygen species was evaluated in the cell-free assay. The used three cell lines showed comparable toxicity responses to NPs and their metal ion counterparts in the current test setting. Six MeOx NPs (Al2O3, Fe3O4, MgO, SiO2, TiO2, WO3) did not show toxic effects below 100 µg/mL. For five MeOx NPs, the averaged 24 h IC50 values for the three mammalian cell lines were 16.4 µg/mL for CuO, 22.4 µg/mL for ZnO, 57.3 µg/mL for Sb2O3, 132.3 µg/mL for Mn3O4 and 129 µg/mL for Co3O4. Comparison of the dissolution level of MeOx and the toxicity of soluble salts allowed to conclude that the toxicity of CuO, ZnO and Sb2O3 NPs was driven by release of metal ions. The toxic effects of Mn3O4 and Co3O4 could be attributed to the ROS-inducing ability of these NPs. All the NPs were internalized by the cells according to light microscopy studies but also proven by TEM, and internalization of Co3O4 NPs seemed to be most prominent in this aspect. In conclusion, this work provides valuable toxicological data for a library of 11 MeOx NPs. Combining the knowledge on toxic or non-toxic nature of nanomaterials may be used for safe-by-design approach.
Publisher: Wiley
Date: 25-03-2019
Publisher: Springer Science and Business Media LLC
Date: 22-08-2019
DOI: 10.1038/S41467-019-11762-0
Abstract: Alzheimer’s disease (AD) is the most prevalent form of neurodegenerative disorders, yet no major breakthroughs have been made in AD human trials and the disease remains a paramount challenge and a stigma in medicine. Here we eliminate the toxicity of amyloid beta (Aβ) in a facile, high-throughput zebrafish ( Danio rerio ) model using casein coated-gold nanoparticles (βCas AuNPs). βCas AuNPs in systemic circulation translocate across the blood brain barrier of zebrafish larvae and sequester intracerebral Aβ 42 and its elicited toxicity in a nonspecific, chaperone-like manner. This is evidenced by behavioral pathology, reactive oxygen species and neuronal dysfunction biomarkers assays, complemented by brain histology and inductively coupled plasma-mass spectroscopy. We further demonstrate the capacity of βCas AuNPs in recovering the mobility and cognitive function of adult zebrafish exposed to Aβ. This potent, safe-to-use, and easy-to-apply nanomedicine may find broad use for eradicating toxic amyloid proteins implicated in a range of human diseases.
Publisher: MDPI AG
Date: 03-11-2011
DOI: 10.3390/S111110502
Publisher: Public Library of Science (PLoS)
Date: 30-05-2013
Publisher: Springer Science and Business Media LLC
Date: 16-02-2016
DOI: 10.1038/SREP21274
Abstract: Aggregation of human islet amyloid polypeptide (hIAPP) into fibrils and plaques is associated with pancreatic β-cell loss in type 2 diabetes (T2D). However, due to the rapidness of hIAPP conversion in aqueous phase, exactly which hIAPP species is responsible for the observed toxicity and through what mechanisms remains ambiguous. In light of the importance of understanding hIAPP toxicity for T2D here we show a biophysical scheme based on the use of a lipophilic Laurdan dye for examining MIN6 cell membranes upon exposure to fresh and oligomeric hIAPP as well as mature amyloid. It has been found that all three hIAPP species, especially fresh hIAPP, enhanced membrane fluidity and caused losses in cell viability. The cell generation of reactive oxygen species (ROS), however, was the most pronounced with mature amyloid hIAPP. The correlation between changes in membrane fluidity and cell viability and their lack of correlation with ROS production suggest hIAPP toxicity is elicited through both physical and biochemical means. This study offers a new insight into β-cell toxicity induced by controlled hIAPP species, as well as new biophysical methodologies that may prove beneficial for the studies of T2D as well as neurological disorders.
Publisher: Springer Science and Business Media LLC
Date: 26-09-2019
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7CS00372B
Abstract: We highlight the role of molecular self-assembly in eliciting the mesoscopic and pathological properties of amyloid proteins. This knowledge is pivotal for the development of theranostics against amyloid diseases.
Publisher: Elsevier BV
Date: 08-2011
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.TIV.2016.08.004
Abstract: Due to small size and high surface energy nanoparticles (NPs) tend to agglomerate and precipitate. To avoid/diminish that, sonication of NPs stock suspensions prior toxicity testing is often applied. Currently, there is no standardized particle sonication protocol available leading to inconsistent toxicity data, especially if toxicity is driven by NPs' dissolution that may be enhanced by sonication. In this study we addressed the effect of sonication on hydrodynamic size (Dh), dissolution and toxicity of copper oxide (CuO) NPs to mammalian cell line Caco-2 in vitro and bacteria Escherichia coli in the respective test environments (cell culture MEM medium, bacterial LB medium and deionised (DI) water). NPs were suspended using no sonication, water bath and probe sonication with different energy intensities. Increased sonication energy (i) decreased the Dh of CuO NPs in all three test environments (ii) increased dissolution of NPs in MEM medium and their toxicity to Caco-2 (iii) increased dissolution of NPs in LB medium and their bioavailability to E. coli and (iv) had no effect on dissolution and antibacterial effects of NPs in DI water. Thus, to reduce variations in dissolution and toxicity, we recommend sonication of NPs in DI water following the dilution into suitable test media.
Publisher: American Chemical Society (ACS)
Date: 14-11-2017
Publisher: Wiley
Date: 07-10-2018
Publisher: Elsevier BV
Date: 2019
Publisher: American Chemical Society (ACS)
Date: 28-08-2019
Publisher: American Chemical Society (ACS)
Date: 07-01-2020
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.ENVPOL.2012.05.009
Abstract: The sub-toxic effects of CuO nanoparticles (nano-CuO) were evaluated using three recombinant luminescent Escherichia coli bacteria responding specifically to (i) reactive oxygen species (ROS), (ii) single-stranded DNA breaks and (iii) bioavailable Cu ions. Using these sensors we showed that nano-CuO induces the formation of superoxide anions, hydrogen peroxide and single-stranded DNA already at very low sub-toxic levels (0.1 mg Cu/L). The maximal sub-toxic response of all biosensors to nominal concentrations of nano-CuO, micro-CuO (size control) and CuSO(4) (solubility control) occurred at ~6, ~600 and ~0.6 mg Cu/L, respectively. According to the chemical analysis all the latter concentrations yielded ~0.6 mg of soluble Cu/L, indicating that dissolution of CuO particles was the key factor triggering the ROS and DNA damage responses in bacteria. Cu-ions chelation studies also showed that CuO particles were not involved in these stress responses. The solubilization results were confirmed by Pseudomonas fluorescens Cu-ion sensor.
No related grants have been discovered for Aleksandr Kakinen.