Nanoparticles, lung injury, and the role of oxidant stress

Abstract

The emergence of engineered nanoscale materials has provided significant advancements in electronic, biomedical, and material science applications. Both engineered nanoparticles and nanoparticles derived from combustion or incidental processes exhibit a range of physical and chemical properties that induce inflammation and oxidative stress in biological systems. Oxidative stress reflects the imbalance between the generation of reactive oxygen species and the biochemical mechanisms to detoxify and repair the damage resulting from reactive intermediates. This review examines current research on incidental and engineered nanoparticles in terms of their health effects on lungs and the mechanisms by which oxidative stress via physicochemical characteristics influences toxicity or biocompatibility. Although oxidative stress has generally been thought of as an adverse biological outcome, this review also briefly discusses some of the potential emerging technologies to use nanoparticle-induced oxidative stress to treat disease in a site-specific fashion.

Figure 1

Nanoparticles exhibit intrinsic oxidant-generating properties. Nanoparticles may contain transition metals due to particle engineering or as a by-product capable of generating ROS through Fenton-like chemical reactions. Free radical intermediates present on reactive nanoparticle surfaces and redox active groups (e.g., quinones) on nanoparticles are capable of redox cycling producing superoxide or hydroxyl radicals. Nanoparticles with semiconductor properties are capable of generating superoxide via electron jumping from the conduction band to oxygen and photocatalytic capable nanoparticles facilitate the creation of electron-hole pairs generating ROS such as superoxide or hydroxyl radicals. Also, nanoparticles generate and contribute to oxidative stress through direct and indirect cellular interactions. Nanoparticle interaction and damage to internal cellular structures such as lysosomes, mitochondria and the nucleus, can lead to cellular damage and oxidative stress. Through direct gene interaction with nanoparticles or nuclear oxidative stress, activation of signaling pathways for antioxidant or pro-oxidant responses may be up-regulated. Additionally, nanoparticles may indirectly interact with cells to alter ROS production and emission through modified cellular phagocytic activity and oxidative burst.

Figure 2

Oxidative stress reflects the imbalance between the generation of ROS and the biochemical mechanisms to detoxify and repair resulting damage of reactive intermediates. Antioxidant defense, inflammation, and toxicity follow a continuum from adaption and compensation of oxidant stresses to an in equilibrium whereby the protective antioxidant mechanisms breakdown or are overwhelmed.

Figure 3

Bright field (A) and polarized field (B) images of a first generation respiratory bronchiole from a human lung of a 32 year old farm laborer. The inset in panel A and shown in panel B contains numerous polarized particles within intraluminal macrophages as well as within the walls of the respiratory bronchiole and adjacent alveoli. (Reproduced by permission, Environmental Health Perspectives)

Figure 4

Light micrographs of contiguous first-, second- and third-generation respiratory bronchioles from the human lung showing the normal structural anatomy (A) and marked alterations (B) due to increased amounts of interstitial collagen, smooth muscle and visible pigment. These structural changes are most dramatic in the first generation respiratory bronchiole with a progressive decrease in more distal generations. (Reproduced by permission, Environmental Health Perspectives)