Differential hERG ion channel activity of ultrasmall gold nanoparticles

Leifert, Annika; Pan, Yu; Kinkeldey, Anne; Schiefer, Frank; Setzler, Julia; Scheel, Olaf; Lichtenbeld, Hera C.; Schmid, Günter; Wenzel, Wolfgang; Jahnen-Dechent, Willi; Simon, Ulrich

doi:10.1073/pnas.1220143110

Cited by 66 publications

(55 citation statements)

References 36 publications

(36 reference statements)

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“…For instance, only changing the strength of ligand affinity to the nanoparticle, without changing its size or charge, significantly affects the toxicity even for gold nanoparticles. This difference in soft and hard ligand corona effect has been recently reported and confirmed by molecular modelling to be caused by the blocking of ion channels by gold nanoparticles in embryonic kidney cells, with a stronger bio-response for the nanoparticles with the weaker bound ligands [39]. In organisms as sensitive as developing embryos even minute amounts of toxic material may have an impact and therefore cannot be excluded as a reason for the differences between the studies.…”

Section: Discussionmentioning

confidence: 75%

Injection of ligand-free gold and silver nanoparticles into murine embryos does not impact pre-implantation development

Taylor¹,

Garrels²,

Barchanski³

et al. 2014

Beilstein J. Nanotechnol.

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SummaryIntended exposure to gold and silver nanoparticles has increased exponentially over the last decade and will continue to rise due to their use in biomedical applications. In particular, reprotoxicological aspects of these particles still need to be addressed so that the potential impacts of this development on human health can be reliably estimated. Therefore, in this study the toxicity of gold and silver nanoparticles on mammalian preimplantation development was assessed by injecting nanoparticles into one blastomere of murine 2 cell-embryos, while the sister blastomere served as an internal control. After treatment, embryos were cultured and embryo development up to the blastocyst stage was assessed. Development rates did not differ between microinjected and control groups (gold nanoparticles: 67.3%, silver nanoparticles: 61.5%, sham: 66.2%, handling control: 79.4%). Real-time PCR analysis of six developmentally important genes (BAX, BCL2L2, TP53, OCT4, NANOG, DNMT3A) did not reveal an influence on gene expression in blastocysts. Contrary to silver nanoparticles, exposure to comparable Ag+-ion concentrations resulted in an immediate arrest of embryo development. In conclusion, the results do not indicate any detrimental effect of colloidal gold or silver nanoparticles on the development of murine embryos.

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Section: Discussionmentioning

confidence: 75%

Injection of ligand-free gold and silver nanoparticles into murine embryos does not impact pre-implantation development

Taylor¹,

Garrels²,

Barchanski³

et al. 2014

Beilstein J. Nanotechnol.

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“…The first and foremost consideration in selecting surface coating materials is that they should be biocompatible and non-toxic. For example, phosphine-stabilized AuNPs having size of 1.4 nm have been prepared but failed electrophysiologybased safety testing in human embryonic kidney cells, a safety test prescribed in FDA guideline (56). In addition, leaching of such surface coating materials may be problematic such as toxicity caused by cetyltrimethyl ammonium bromide CTAB, a famous stabilizing agent for AuNPs (57).…”

Section: Surface Chemistrymentioning

confidence: 99%

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

et al. 2016

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-Nanotechnology has opened a new horizon of research in various fields including applied physics, chemistry, electronics, optics, robotics, biotechnology and medicine. In the biomedical field, nanomaterials have shown remarkable potential as theranostic agents. Materials which are considered inert are often used in nanomedicine owning to their nontoxic profile. At nanoscale, these inert materials have shown unique properties that differ from bulk and dissolved counterparts. In the case of metals, this unique behavior not only imparts paramount advantages but also confers toxicity due to their unwanted interaction with different cellular processes. In the literature, the toxicity of nanoparticles made from inert materials has been investigated and many of these have revealed toxic potential under specific conditions. The surge to understand underlying mechanism of toxicity has increased and different means have been employed to overcome toxicity problems associated with these agents. In this review, we have focused nanoparticles of three inert metallic materials i.e. gold, silver and iron as these are regarded as biologically inert in the bulk and dissolved form. These materials have gained wider research interest and studies indicating the toxicity of these materials are also emerging. Oxidative stress, physical binding and interference with intracellular signaling are the major role player in nanotoxicity and their predominance is highly dependent upon size, surface coating and administered dose of nanoparticles. Current strategies to overcome toxicity have also been reviewed in the light of recent literature. The authors also suggested that uniform testing standards and well-designed studies are needed to evaluate nanotoxicity of these materials that are otherwise considered as inert.

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“…In a more recent study, ultrasmall gold nanoparticles were shown to irreversibly block hERG channels in patchclamp recordings (21). hERG forms the alpha subunit of one of the ion channel proteins that conducts potassium (K + ) ions in the heart.…”

Section: Towards a Molecular Nanotoxicologymentioning

confidence: 99%

Keeping it small: towards a molecular definition of nanotoxicology

Gallud

Fadeel

2015

European Journal of Nanomedicine

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Abstract:In this essay, we offer the opinion that engineered nanomaterials are, by definition, materials that can interact with biological systems at the nanoscale, and that this very fact underlies both the promise and the peril of this multifaceted class of materials. Furthermore, nanomaterials are cloaked in host-derived proteins, lipids, or other biomolecules as they enter into a living organism and this so-called bio-corona may impact on subsequent interactions with biological structures. We will explore some examples of nanoscale effects of engineered nanomaterials, and discuss how such interactions may underpin toxicity, and, conversely, how nanoscale interactions may be harnessed for clinical applications, including the use of nanoparticles as drugs per se.Keywords: biological mimicry; cellular nanomachineries; engineered nanomaterials; molecular dynamics simulations; nanomedicine; nanotopographies; nanotoxicology. Life is a nanoscale phenomenonIn their seminal paper published one decade ago, Donaldson et al. (1) proposed that a new subcategory of toxicology -namely nanotoxicology -be defined to specifically address "the special problems likely to be caused by nanoparticles", and the authors suggested that nanotoxicology be considered "a new frontier in particle toxicology". However, one may argue, instead, that nanotoxicology represents a departure from the traditional toxicology of fine and ultrafine particles and fibers. In fact, nanotoxicology may be understood in light of "the interference of engineered nanomaterials with the functions of cellular and extracellular nanomachineries" (2). This view places emphasis on the fact that life (biology) is "a nanoscale phenomenon" (3). Indeed, living organisms are host to a range of dedicated intra-and extracellular nanoscale machines (4) and this, therefore, suggests that specific, size-dependent toxicities may ensue as a result of exposure to engineered nanomaterials. This does not, however, mean that all nanomaterials are inherently toxic (5), or that a nanospecific effect is necessarily detrimental to the host; in fact, the controlled manipulation of biological systems at the nanoscale may very well open up for novel therapeutic approaches. In this essay, we will explore both sides of the coin. The right size in nanotoxicologyIn his review on "the 'right' size in nanobiotechnology", Whitesides argued that "small" -both nano and micromust be a part of the future of biotechnology; which size is most important depends on what question one is asking (6). Surprisingly, in the field of nanotoxicology, the question of size, and more specifically, how one should define a nanomaterial (indeed, whether or not one should define nanomaterials in the first place) remains a matter of debate. Hence, while some have argued that we should not define nanomaterials, or to be more precise, that a 'one-size-fitsall' definition of nanomaterials will fail to capture what is important for addressing risk (7), others have stated that a definition of nanomaterials for regulatory ...

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Differential hERG ion channel activity of ultrasmall gold nanoparticles

Cited by 66 publications

References 36 publications

Injection of ligand-free gold and silver nanoparticles into murine embryos does not impact pre-implantation development

Injection of ligand-free gold and silver nanoparticles into murine embryos does not impact pre-implantation development

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

Keeping it small: towards a molecular definition of nanotoxicology

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