Toxicity of metal-based nanoparticles: Challenges in the nano era

Abstract

With the rapid progress of nanotechnology, various nanoparticles (NPs) have been applicated in our daily life. In the field of nanotechnology, metal-based NPs are an important component of engineered NPs, including metal and metal oxide NPs, with a variety of biomedical applications. However, the unique physicochemical properties of metal-based NPs confer not only promising biological effects but also pose unexpected toxic threats to human body at the same time. For safer application of metal-based NPs in humans, we should have a comprehensive understanding of NP toxicity. In this review, we summarize our current knowledge about metal-based NPs, including the physicochemical properties affecting their toxicity, mechanisms of their toxicity, their toxicological assessment, the potential strategies to mitigate their toxicity and current status of regulatory movement on their toxicity. Hopefully, in the near future, through the convergence of related disciplines, the development of nanotoxicity research will be significantly promoted, thereby making the application of metal-based NPs in humans much safer.

Keywords: assessment; mechanism; metal-based nanoparticle; mitigation; nanotoxicity; physicochemical property; regulatory movement.

FIGURE 1

Physicochemical Properties Affecting metal-based NP Toxicity. Different Sizes, shapes, chemical compositions, surface chemistry, solubility and agglomeration are closely related to the toxicity induced by metal-based NPs.

FIGURE 2

Mechanisms of cell damage by metal-based NPs. Following cellular uptake of NPs, metal-based NPs can release intracellular metal ions and induce oxidative stress directly or through mitochondrial dysfunction. ROS generation and consequent oxidative stress are shown to be the fundamental cause of metal-based NP toxicity. The excessive ROS generation and metal ions impact multiple cell signaling pathways, mainly including JAK-STAT, NF-κB, PI3K/Akt, MAPK, Nrf2. ROS can also cause DNA damage. Thus, it hinders cell physiological processes like proliferation and differentiation, eventually leading to cell apoptosis or necrosis.

FIGURE 3

Strategies to mitigate metal-based NP toxicity. Surface coating, surface chemistry modifications by altering charge density and hydrophobicity, and introducing naturally derived cell membranes from several cell types can be used to reduce the potential toxicity of metal-based NPs.