Nanotoxicology: Toxicity and Biological Effects of Nanoparticles for New Evaluation Standards

Despite the emerging sense that well-engineered, novel-property nanomaterials will continue to be studied and will be utilized to a greater extent in the future for a wide range of biomedical applications, there is also a growing concern that unusual and unexpected toxicity may arise from desired properties, such as higher reactivity, unusual complex shapes, and accessibility to cells, which man-made materials possess in the nanoscale [1–14]. Therefore, it is essential to establish a new toxicology study that deviates from or modifies conventional methods.

It is difficult to adequately assess the biological effects of nanoparticles due to the fact that their cellular uptake, in vivo behavior and excretion are controlled by numerous factors. Any change in the composition, size, morphology, route of exposure or dosage can significantly affect the immunological response and toxic effects elicited by the nanoparticle. Additionally, these properties can affect the outcome of a particular cytotoxicity or toxicological assay due to unforeseen interferences and inadequate controls.

In this respect, this special focus issue of Nanomedicine will provide the chance to read and discuss the most recent and significant research efforts toward nanotoxicology in the aspects of new methods, biological models, and experimental concerns. Drezek and colleagues have provided an extensive review on the current status of nanoparticle biodistribution and toxicity studies [15]. The authors discuss the need for long-term in vivo studies to fully investigate the toxicity, immune response and excretion over time of nanoparticles, and the need for a more systematic approach toward in vitro experiments for improved correlation between nanoparticle properties and observed effects. To address the safety standards of new emerging nanotechnology, a review by Krug and colleagues discusses the current reliability of in vitro toxicity assays as well as major problems and challenges of assay performance and validation in which the group recommends a series of controls to improve experimental quality that will increase the safe and sustainable use of nanotechnology for the future [16]. In addition, a review by Lee and colleagues highlights the most significant factors affecting nanoparticle cytotoxicity assays and the improved experimental considerations needed to address them in order to gain reliable data and better define the adverse effects of nanoparticles [17]. A review by Porter and colleagues discusses the challenges associated with characterizing the toxicity of carbon nanotubes and the need for complementary nanometrology to relate their physiochemical properties with their toxicity [18]. The authors suggest a combination of high resolution electron microscopy techniques and cell viability assays to understand cytotoxic mechanisms of the targeting site and stability of carbon nanotubes inside cells and tissues. With regard to specific classes of nanomaterials, Fubini discusses the various types of high-aspect ratio nanoparticles, focusing on the most relevant characteristics that lead to their toxic effects [19]. The author states that similarities in form or composition are not adequate to establish toxicity and that the effect of size, form, durability, composition and surface modification must be investigated for all high-aspect ratio nanoparticles. Choy and Choi provide an overview of the cellular uptake mechanism, behavior and toxicity of layered double hydroxides both in vitro and in vivo, focusing on the effect of physiochemical properties, dosage and interaction with biological systems on biocompatibility [20]. A research article by Zhang, Bäumer and Monteiro-Riviere explores the toxicity and cellular uptake of quantum dots by dendritic cells, shedding new light on the dependence of cellular uptake pathways on cell type and cell differentiation [21]. Garcia-Bennett gives an overview of ordered mesoporous nanomaterials for use in nanomedicine applications, concentrating on the high surface area and pore volume, loading and release ability, and low immunotoxicological behavior of these nanoparticles [22]. Stensberg and coworkers provide an intense discussion on the recent research on the transport, activity and fate of silver nanoparticles at the cellular and organism level in conjunction with traditional and recently established methods of nanoparticle characterization [23]. The authors propose several mechanisms of cytotoxcity based on such studies, as well as new opportunities for investigating the uptake and fate of silver nanoparticles, establishing better models to assess long-term effects in vivo.

Research focused on improving biocompatibility and limiting toxicity with novel nanoparticles is also presented in this issue. Chan and Chou discuss a strategy for the coassembly of hydrophobic nanoparticles with amphiphilic polymers that minimizes cytotoxicity and enhances stability of the nanoparticle due to the protective polymeric shell [24]. Lee, Lee and coworkers talk about their recent successful evaluation of the in vivo biocompatibility of polydopamine focusing on blood immunogenicity and tissue inflammation [25]. The group found that polydopamine can provide a biocompatible nanocoating for material surfaces that would otherwise exhibit certain degrees of toxicity. Lee and colleagues provide a perspective on the use of nanoparticles as a method of removing toxic species from the body and discuss their recent research on silica nanotubes as a platform for the chemical oxidation and reduction of reactive, toxic compounds [26].

Given the increasing attention in both the development of new functional nanomaterials and the health and environmental concerns of those materials, researchers in this field are responsible for the understanding of the complete physicochemical properties of the nanomaterials and for developing new nanotoxicological standards. It is likely to take a long time (10 years or more) to establish the new standards and to have a consensus in this field. However, this must not cause any delay in seeking new nanomedicinal technologies.

Financial & competing interests disclosure

SB Lee thanks the support of the WCU program of the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (grant number: R31-2008-000-10071-0). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

SB Lee thanks the support of the WCU program of the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (grant number: R31-2008-000-10071-0). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.