Metal Nanomaterial Toxicity Variations Within the Vascular System

Abstract

Engineered nanomaterials (ENM) are anthropogenic materials with at least one dimension less than 100 nm. Their ubiquitous employment in biomedical and industrial applications in the absence of full toxicological assessments raises significant concerns over their safety on human health. This is a significant concern, especially for metal and metal oxide ENM as they may possess the greatest potential to impair human health. A large body of literature has developed that reflects adverse systemic effects associated with exposure to these materials, but an integrated mechanistic framework for how ENM exposure influences morbidity remains elusive. This may be due in large part to the tremendous diversity of existing ENM and the rate at which novel ENM are produced. In this review, the influence of specific ENM physicochemical characteristics and hemodynamic factors on cardiovascular toxicity is discussed. Additionally, the toxicity of metallic and metal oxide ENM is presented in the context of the cardiovascular system and its discrete anatomical and functional components. Finally, future directions and understudied topics are presented. While it is clear that the nanotechnology boom has increased our interest in ENM toxicity, it is also evident that the field of cardiovascular nanotoxicology remains in its infancy and continued, expansive research is necessary in order to determine the mechanisms via which ENM exposure contributes to cardiovascular morbidity.

Keywords: Cardiovascular system; Engineered nanomaterials; Metal; Metal oxides; Microcirculation.

Figure 1

Schematic representation of the cardiopulmonary system and identification of locations for ENM influences/activities. Black arrows: blood flow direction. Red represents oxygenated blood. Blue represents deoxygenated blood. 1) Extrapulmonary translocation to systemic circulation. 2) Arterial bifurcation and impaction. 3) Eddy current turbulence and impaction. 4) Segre-Silberg effect and plasma settling. 5) Systemic capillary translocation and tissue deposition. 6) Venular inflammatory signaling. 7) Venous settling. For simplicity, only one systemic tissue is depicted.