Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Setyawati, Magdiel Inggrid; Tay, Chor Yong; Chia, Sing Ling; Goh, Seok-Hong; Fang, Wanru; Neo, M.; Chong, Han Chung; Tan, Suet-Mien; Loo, Say Chye Joachim; Ng, Kee Woei; Xie, Jianping; Ong, Choon Nam; Tan, Nguan Soon; Leong, David Tai

doi:10.1038/ncomms2655

Cited by 404 publications

(314 citation statements)

References 40 publications

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“…50 The biodistribution of the three different surface-charge variants could reflect typical renal clearance of NCs, while the biphasic distribution suggested that NCs can be easily retained in the tissues or organs through the endothelial leakiness effect. 51 The target selectivity of Au NCs with different surface charges is consistent with the in vivo biodistribution of Au composite nanodevices (5 nm) with different surface charges. 47 …”

supporting

confidence: 66%

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Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy

Wang

Chen

Yang

et al. 2016

IJN

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Gold nanoclusters (Au NCs) have exhibited great advantages in medical diagnostics and therapies due to their efficient renal clearance and high tumor uptake. The in vivo effects of the surface chemistry of Au NCs are important for the development of both nanobiological interfaces and potential clinical contrast reagents, but these properties are yet to be fully investigated. In this study, we prepared glutathione-protected Au NCs of a similar hydrodynamic size but with three different surface charges: positive, negative, and neutral. Their in vivo biodistribution, excretion, and toxicity were investigated over a 90-day period, and tumor uptake and potential application to radiation therapy were also evaluated. The results showed that the surface charge greatly influenced pharmacokinetics, particularly renal excretion and accumulation in kidney, liver, spleen, and testis. Negatively charged Au NCs displayed lower excretion and increased tumor uptake, indicating a potential for NC-based therapeutics, whereas positively charged clusters caused transient side effects on the peripheral blood system.

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supporting

confidence: 66%

“…51 However, fast renal clearance can undermine the potential for distribution in the tumor tissue. The high tumor uptake of positive Au NCs has been attributed to rapid extrication into the interstitium and internalization into the endothelium.…”

mentioning

confidence: 99%

Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy

Wang

Chen

Yang

et al. 2016

IJN

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“…In a particularly illustrative study, Setyawati et al (32) provided evidence that spherical TiO 2 nanoparticles (23.5 nm) caused endothelial cell leakiness in an in vitro model using human microvascular endothelial cells. This was suggested to occur through the physical interaction between the nanoparticles and the adherens junction protein VEcadherin.…”

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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“…Safety concerns about nano-TiO 2 -based products have been raised. [123][124][125] Reports suggest that TiO 2 nanoparticles do not penetrate the intact epidermal barrier, [126,127] with no evidence of significant penetration beyond the stratum corneum. [128] Melanin is used in cosmetic products, sometimes in combination with photoactive oxides.…”

Section: Melanin/metal Oxides Interfaces: Adhesion Biocompatibilitymentioning

confidence: 99%

Natural melanin pigments and their interfaces with metal ions and oxides: emerging concepts and technologies

Mauro

Soliveri

et al. 2017

MRS Communications

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Melanin (from the Greek μέλας, mélas, black) is a biopigment ubiquitous in flora and fauna, featuring broadband optical absorption, hydration-dependent electrical response, ion-binding affinity as well as antioxidative and radical-scavenging properties. In the human body, photoprotection in the skin and ion flux regulation in the brain are some biofunctional roles played by melanin. Here we discuss the progress in melanin research that underpins emerging technologies in energy storage/conversion, ion separation/water treatment, sunscreens, and bioelectronics. The melanin research aims at developing approaches to explore natural materials, well beyond melanin, which might serve as a prototype benign material for sustainable technologies.

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Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Cited by 404 publications

References 40 publications

Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy

Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy

Keeping it small: towards a molecular definition of nanotoxicology

Natural melanin pigments and their interfaces with metal ions and oxides: emerging concepts and technologies

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