ABSTRACT
Newly developed nanomaterials are being increasingly used in industrial applications and in medicine as cutting-edge tools for therapeutic and diagnostic applications in biomedicine (e.g., highly sensitive and stable probes to detect changes in intracellular molecules) (Cuenca et al. 2006), early detection and diagnosis (Freitas 2005), and targeted delivery of therapeutics to specic cell types (Cuenca et al. 2006; Freitas 2005). Pulmonary delivery of nanomaterials may have certain advantages owing to the large surface area for absorption and the limited proteolytic activity (Sung et al. 2007) of the lungs. Nanoparticles (NPs) can be delivered locally for the treatment of lung diseases, such as cancer, asthma, or cystic brosis (Sermet-Gaudelus et al. 2002; Sung et al. 2007). This targeted delivery can potentially result in reducing the overall dose and side effects that result from high levels of systemic exposure. Alternatively, systemic delivery can be achieved by targeting delivery to the alveolar region where the drug can be absorbed through the thin layer of epithelial lining cells into the systemic circulation (Patton et al. 2004; Patton and Byron 2007; Sung et al. 2007). This approach may be desirable to achieve a rapid onset of action, avoidance
CONTENTS
7.1 Introduction ........................................................................................................................ 107 7.2 Overview on Health Effects ............................................................................................. 108
7.2.1 Health Effects of Ambient Ultrane Particles (AUFP) and ENM ................... 108 7.2.2 Carbonaceous NP-Induced Toxicity in Lung Cells/Tissues ............................ 110 7.2.3 QD-Induced Toxicity in Lung Cells/Tissues ..................................................... 112 7.2.4 Silica NP-Induced Toxicity in Lung Cells/Tissues ............................................ 113 7.2.5 Metal Nanoparticle (MNP) or Metal Oxide Nanoparticle (MONP)
Toxicity in Lung Cells/Tissues ............................................................................ 113 7.3 Mechanisms Underlying ENM-Induced Toxicity and Injury to Cells ....................... 114 7.4 Mechanisms Underlying ENM Trafcking ................................................................... 115
7.4.1 Endocytic Processes............................................................................................... 116 7.4.2 Nonendocytic Mechanisms .................................................................................. 117
7.5 Nanomaterial Interactions with Primary Rat/Mouse AEC Monolayers ................... 118 7.6 Summary ............................................................................................................................. 120 Acknowledgments ...................................................................................................................... 120 References ..................................................................................................................................... 121
of rst-pass metabolism, and delivery of biotherapeutics that cannot be effective orally (owing to enzymatic degradation and/or poor intestinal membrane permeability) as an alternative to parenteral delivery (Hamman et al. 2005).
