Keeping it small: towards a molecular definition of nanotoxicology

Abstract

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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