Nanotoxicology: Advances and Pitfalls in Research Methodology

Abstract

As research progresses, nanoparticles (NPs) are becoming increasingly promising tools for medical diagnostics and therapeutics. Despite this rise, their potential risks to human health, together with environmental issues, has led to increasing concerns regarding their use. As such, a comprehensive understanding of the interactions that occur at the nano-bio interface is required in order to design safe, reliable and efficient NPs for biomedical applications. To this end, extensive studies have been dedicated to probing the factors that define various properties of the nano-bio interface. However, the literature remains unclear and contains conflicting reports on cytotoxicity and biological fates, even for seemingly identical NPs. This uncertainty reveals that we frequently fail to identify and control relevant parameters that unambiguously and reproducibly determine the toxicity of nanoparticles, both in vitro and in vivo. An effective understanding of the toxicological impact of NPs requires the consideration of relevant factors, including the temperature of the target tissue, plasma gradient, cell shape, interfacial effects and personalized protein corona. In this review, we discuss the factors that play a critical role in nano-bio interface processes and nanotoxicity. A proper combinatorial assessment of these factors substantially changes our insight into the cytotoxicity, distribution and biological fate of NPs.

Protein corona: Opportunities and challenges

“…There are still many unmet challenges that are required before the design of truly efficient targeted nanoparticles is attained. Additionally, more work is needed to ensure predictable biological and in vivo outcomes (Azhdarzadeh et al, 2015a; Mahon et al, 2012). Should this goal be accomplished, it could potentially revolutionize multiple therapeutic areas and make significant improvements in nanomedicine (Saie et al, 2015).…”

“…Most of the toxicological protocols used for nanoparticles were developed decades before the first nano-based publication came out (Azhdarzadeh et al, 2015b). This means that these approaches are not specifically designed for toxicity evaluation of nanoparticles.…”

“…Several studies also demonstrated that addressing several factors including the temperature of the target tissue, plasma gradient, cell shape, interfacial effects, and personalized protein corona, could improve consistency of toxicity results between laboratories (Azhdarzadeh et al, 2015a). Thus when these factors are taken into consideration, in vitro assays have the capacity to be reliable predictors of in vivo behavior.…”

Current Challenges toward In Vitro Cellular Validation of Inorganic Nanoparticles

“…53−57 We refer the reader to several review articles which address in detail common pitfalls while assessing NP cytotoxicity, with special reference to intracellular changes. 10,58,59 …”

Assessment of food toxicology

“…The discipline of environmental toxicology is related to studies of various chemical, biological and physical agents which are harmful to humans, whereas regulatory toxicology is concerned with risk assessment of food and potential toxicants [51,162]. By virtue of advances in nanotechnology and its application in food industry, the newly created discipline of nanotoxicology investigates safety or potential hazards of nanoparticles [52,[163][164][165]. Another dimension refers to genetically modified organisms (GMO) or food (GM) as potential source of toxicity [52,166,167].…”