Abuelmagd M. Abdelmonem

In vivo integrity of polymer-coated gold nanoparticles

Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties may change upon internalization by cells. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles ((198)Au) and engineered an (111)In-labelled polymer shell around them. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for (198)Au and (111)In showed partial removal of the polymer shell in vivo. While (198)Au accumulates mostly in the liver, part of the (111)In shows a non-particulate biodistribution similar to intravenous injection of chelated (111)In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo.

Multiplexed Sensing and Imaging with Colloidal Nano- and Microparticles

Sensing and imaging with fluorescent, plasmonic, and magnetic colloidal nano- and microparticles have improved during the past decade. In this review, we describe the concepts and applications of how these techniques can be used in the multiplexed mode, that is, sensing of several analytes in parallel or imaging of several labels in parallel.

The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

Colloidal semiconductor nanoparticles (quantum dots) have attracted a lot of interest in technological and biomedical research, given their potent fluorescent properties. However, the use of heavy-metal-containing nanoparticles remains an issue of debate. The possible toxic effects of quantum dots remain a hot research topic and several questions such as possible intracellular degradation of quantum dots and the effect thereof on both cell viability and particle functionality remain unresolved. In the present work, amphiphilic polymer [corrected] coated CdSe/ZnS quantum dots were synthesized and characterized, after which their effects on cultured cells were evaluated using a multiparametric setup. The data reveal that the quantum dots are taken up through endocytosis and when exposed to the low pH of the endosomal structures, they partially degrade and release cadmium ions, which lowers their fluorescence intensity and augments particle toxicity. Using the multiparametric method, the quantum dots were evaluated at non-toxic doses in terms of their ability to visualize labeled cells for longer time periods. The data revealed that comparing different particles in terms of their applied dose is challenging, likely due to difficulties in obtaining accurate nanoparticle concentrations, but evaluating particle toxicity in terms of their biological functionality enables an easy and straightforward comparison.

Charge and agglomeration dependent in vitro uptake and cytotoxicity of zinc oxide nanoparticles

The influence of the surface charge and the state of agglomeration of ZnO nanoparticles on cellular uptake and viability are investigated. For this purpose, ZnO nanoparticles were synthesized by colloidal routes and their physicochemical properties were investigated in detail. Three different surface modifications were investigated, involving coatings with the amphiphilic polymer poly(isobutylene-alt-maleic anhydride)-graft-dodecyl, mercaptoundecanoic acid, and L-arginine, which provide the nanoparticles with either a negative or a positive zeta-potential. The hydrodynamic diameters and zeta-potentials of all three nanoparticle species were investigated at different pH values and NaCl concentrations by means of dynamic light scattering and laser Doppler anemometry, respectively. The three differently modified ZnO nanoparticle species of similar sizes were also investigated in respect to their cellular uptake by 3T3 fibroblasts and HeLa cells, and their effect on cell viability.

Photoelectrochemical Sensor Based on Quantum Dots and Sarcosine Oxidase

In this study, a photobioelectrochemical sensor for the detection of sarcosine is reported. For this purpose, CdSe/ZnS quantum dot (QD) modified electrodes are prepared and the oxygen-dependent photocurrent is evaluated under illumination. By using sarcosine oxidase (SOD), the photocurrent can be suppressed because of biocatalytic oxygen reduction. For the construction of a sensor, SOD is immobilised on the QDs by means of the polyelectrolyte poly(allylamine hydrochloride) (PAH). Multi-layer systems have been built up to six bilayers through electrostatic interactions. The assembly can be verified by surface plasmon resonance measurements. By varying the number of layers, the influence of the amount of enzyme on the sensitivity of the sensor can be shown. The [SOD/PAH]6-layer system results in a signal change of 0.041% μM(-1) in the linear range from 100 μM to 1 mM of sarcosine.

Evaluation of quantum dot cytotoxicity: interpretation of nanoparticle concentrations versus intracellular nanoparticle numbers

Abstract While substantial progress has been achieved in the design of more biocompatible nanoparticles (NP), detailed data are required on the precise interactions of NPs and their environment for more reliable interpretation of toxicity results. Therefore, this study aims to investigate the interaction of two quantum dots (QDs) of the same core material CdSe/ZnS coated with two different amphiphilic polymers, with two well-established mammalian cell lines representing possible sites of QD accumulation. Results are linked to either extracellular QD concentrations (given dose) or cellular QD levels (number of internalized particles). In this study, QD internalization, effects on cellular homeostasis, and consequent inflammatory and cytoskeletal alterations caused by these QDs were explored. Fluorescence imaging techniques, including; image-based flow cytometry, confocal microscopy and high-content imaging with the InCell analyzer were used in a multiparametric methodology to evaluate cell viability, induction of oxidative stress, mitochondrial health, cell cytoskeletal functionality and changes in cellular morphology. Gene expression arrays were also carried out on 168 key genes involved in the cytoskeletal architecture and inflammatory pathway accompanied with the analysis of focal adhesions as key markers for actin-mediated signaling. Our results show distinct differences between the PMA and PTMAEMA-stat-PLMA coated QDs, which could mainly be attributed to differences in their cellular uptake levels. The toxicity profiles of both QD types changed drastically depending on whether effects were expressed in terms of given dose or internalized particles. Both QDs triggered alterations to important but different genes, most remarkably the up-regulation of tumor suppression and necrosis genes and the down regulation of angiogenesis and metastasis genes at sub-cytotoxic concentrations of these QDs.

Dissecting common and divergent molecular pathways elicited by CdSe/ZnS quantum dots in freshwater and marine sentinel invertebrates

Abstract Water ecosystems represent main targets of unintentional contamination of nanomaterials, due to industrial waste or other anthropogenic activities. Nanoparticle insult to living organisms may occur in a sequential way, first by chemical interactions of the material with the target membrane, then by progressive internalisation and interaction with cellular structures and organelles. These events trigger a signal transduction, through which cells modulate molecular pathway in order to respond and survive to the external elicitation. Therefore, the analysis of the global changes of the molecular machinery, possibly induced in an organism upon exposure to a given nanomaterial, may provide unique clues for proper and exhaustive risk assessment. Here, we tested the impact of core/shell CdSe/ZnS QDs coated by a positively charged polymer on two aquatic species, the polyp Hydra vulgaris and the coral S. pistillata, representative of freshwater and sea habitats, respectively. By using reliable approaches based on animal behaviour and physiology together with a whole transcriptomic profiling, we determined several toxicity endpoints. Despite the difference in the efficiency of uptake, both species were severely affected by QD treatment, resulting in dramatic morphological damages and tissue bleaching. Global transcriptional changes were also detected in both organisms, but presenting different temporal dynamics, suggesting both common and divergent functional responses in the two sentinel organisms. Due to the striking conservation of structure and genomic organisation among animals throughout evolution, our expression profiling offers new clues to identify novel molecular markers and pathways for comparative transcriptomics of nanotoxicity.

Corrigendum to “The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology” [Acta Biomater. 10 (2014) 732–741]

http://dx.doi.org/10.1016/j.actbio.2014.11.008 1742-7061/ 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. DOI of original article: http://dx.doi.org/10.1016/j.actbio.2013.09.041 ⇑ Corresponding author. Tel.: +32 9264 8076; fax: +32 9264 8189. E-mail address: Stefaan.Desmedt@ugent.be (S.C. De Smedt). Stefaan J. Soenen , José-Maria Montenegro , Abuelmagd M. Abdelmonem , Bella B. Manshian , Shareen H. Doak , Wolfgang J. Parak , Stefaan C. De Smedt a,⇑, Kevin Braeckmans a,b