Nanotoxicology and Nanomedicine: The Yin and Yang of Nano-Bio Interactions for the New Decade

Abstract

Nanotoxicology and nanomedicine are two sub-disciplines of nanotechnology focusing on the phenomena, mechanisms, and engineering at the nano-bio interface. For the better part of the past three decades, these two disciplines have been largely developing independently of each other. Yet recent breakthroughs in microbiome research and the current COVID-19 pandemic demonstrate that holistic approaches are crucial for solving grand challenges in global health. Here we show the Yin and Yang relationship between the two fields by highlighting their shared goals of making safer nanomaterials, improved cellular and organism models, as well as advanced methodologies. We focus on the transferable knowledge between the two fields as nanotoxicological research is moving from pristine to functional nanomaterials, while inorganic nanomaterials - the main subjects of nanotoxicology - have become an emerging source for the development of nanomedicines. We call for a close partnership between the two fields in the new decade, to harness the full potential of nanotechnology for benefiting human health and environmental safety.

Keywords: NanoEL; coronavirus; microbiome; nanomedicine; nanotoxicology; protein corona.

Fig. 1.. A meta-analysis of research emphases in nanotoxicology versus nanomedicine.

(Top) Lexicons of nanotoxicology (magenta) and nanomedicine (navy blue), extracted on the 31^st of July, 2020 from two representative journals: Nanotoxicology (Taylor and Francis) and Nanomedicine: Nanotechnology, Biology and Medicine (Elsevier) using Web of Science (Clarivate Analytics). The keywords used for the search (except for “virus” and “microbiome”, which were added as emerging research directions) were selected from the most frequently used words from the Perspectives by Fadeel et al. (2018) [9], Faria et al. (2018) [10] and Pelaz et al. (2017) [11], identified by WordCounter. (Bottom) Similarities and differences between nanotoxicology and nanomedicine research foci, extracted from the top panel.

Fig. 2.

The microbiota profoundly influences the toxicity-therapeutic potential balance of nanomedicines (A). Such complex involvement of the gut microbiota in modulating the efficacy and toxicity of oral nanomedicines remains to be understood (B).

Fig. 3.

Nanotoxicology and nanomedicine may offer mechanistic insights and theranostic solutions for combating emerging novel coronaviruses such as SARS-CoV-2.

Fig. 4.

NM-induced endothelial leakiness (NanoEL) is a tissue level phenomenon originated from nanoscale interactions between NMs and endothelial adherens junctions. Originally established as a nanosafety concept, NanoEL may have huge therapeutic implications for guiding vascular transport and tumor targeting of nanomedicines.

Scheme 1.. Nanotoxicology and nanomedicine, at a glance.

Both fields have been developed largely independently over the past decades, yet both fields are concerned with the fate and behavior of engineered as well biological nanoparticles in biological systems and, as a result, share much in common in terms of their goals, methodologies, and biological model systems. Knowledge transfer from nanotoxicology to nanomedicine, beyond the framework of nanosafety and in the forms of toxicity data, quantitative structure–activity relationship (QSAR) and other nanoinformatics models, modes of action, and responses to NM exposure, would greatly benefit nanomedicine. Conversely, research in nanotoxicology, currently focused on defined NMs, could gain an enhanced purpose and applicability by investigating functional NM hybrids designed for nanomedicine (their safety, interactions with the microbiome and endogenous proteins, as well as the fate and behavior of wear-off NMs from medical devices for example). Here the bold arrows indicate current deficiencies where improvements may be made to benefit the development of both fields. Thin orange arrows denote inputs and thin blue arrows outputs from each field.