Delivered by Publishing Technology to: Deakin University Library IP: 187.16.233.195 On: Wed, 30 Dec 2015 18:40:53 Copyright: American Scientific Publishers Copyright © 2016 American Scientific Publishers All rights reserved Printed in the United States of America Review Journal of Nanoscience and Nanotechnology Vol. 16, 40–57, 2016 www.aspbs.com/jnn Nanomaterial Induced Immune Responses and Cytotoxicity Ashraf Ali 1† , Mohd Suhail 1† , Shilu Mathew 2 , Muhammad Ali Shah 3 4 , Steve M. Harakeh 1 , Sultan Ahmad 1 , Zulqarnain Kazmi 1 , Mohammed Abdul Rahman Alhamdan 5 , Adeel Chaudhary 1 , Ghazi Abdullah Damanhouri 1 , and Ishtiaq Qadri 1 * 1 King Fahd Medical Research Center (KFMRC), King Abdulaziz University, Jeddah, 21589, Saudi Arabia 2 Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, 21589, Saudi Arabia 3 Faculty of Veterinary and Animal Sciences, University of Arid Agricultural, Rawalpindi, 46300, Pakistan 4 School of Biological Science and Medical Engineering, Southeast University 210096, Nanjing, China 5 College of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia Nanomaterials are utilized in a wide array of end user products such as pharmaceuticals, electron- ics, clothes and cosmetic products. Due to its size (<100 nm), nanoparticles have the propensity to enter through the airway and skin, making its path perilous with the potential to cause damages of varying severity. Once within the body, these particles have unconstrained access to different tissues and organs including the brain, liver, and kidney. As a result, nanomaterials may cause the perturbation of the immune system eliciting an inflammatory response and cytotoxicity. This poten- tial role is dependent on many factors such as the characteristics of the nanomaterials, presence or absence of diseases, and genetic predisposition. Cobalt and nickel nanoparticles, for example, were shown to have inflammogenic properties, while silver nanoparticles were shown to reduce aller- gic inflammation. Just as asbestos fibers, carbon nanotubes were shown to cause lungs damage. Some nanomaterials were shown, based on animal studies, to result in cell damage, leading to the formation of pre-cancerous lesions. This review highlights the impact of nanomaterials on immune system and its effect on human health with toxicity consideration. It recommends the development of suitable animal models to study the toxicity and bio-clearance of nanomaterials and propose safety guidelines. Keywords: Nanomaterials, Nanoparticles, Nanotoxicology, Cellular Uptake, Inflammation, Macrophages, Cytochrome P450, Apoptosis, Necrosis, Autophagy, Pyroptosis. CONTENTS 1. Introduction ........................................ 40 2. Entry and Route of Nanomaterials Inside the Body .......... 44 3. Effects of Exposure to Nanomaterials .................... 44 4. Nanomaterial Mediated Oxidative Stress, Inflammation and Genotoxicity ......................... 46 4.1. Oxidative Stress ................................. 46 4.2. Inflammatory Mediators of Stress ................... 46 4.3. Antioxidants .................................... 46 4.4. DNA Damage .................................. 46 5. Induction of Different Inflammatory Reactions ............. 46 6. Nanomaterials and Lung Function ....................... 47 7. Nanomaterial Induced Cytotoxicity ...................... 48 8. Bioaccumulation and Clearance ......................... 50 * Author to whom correspondence should be addressed. † These two authors contributed equally to this work. 9. Regulation of Nanomaterials Delivery .................... 51 10. Conclusion ........................................ 51 Acknowledgments ................................... 52 References and Notes ................................ 52 1. INTRODUCTION The recent development in nanotechnology has provided scientists with new momentum to target diseases that could not be treated traditionally. However, the drive to employ nanomaterials has raised health concerns and risks. Cur- rently, nanotechnology is being implemented in various fields of medicine, where nanomaterials are used in clin- ical and imaging diagnostics, and as drug delivery vehi- cles (see Table I-Nanomaterials and their Application). 1–9 40 J. Nanosci. Nanotechnol. 2016, Vol. 16, No. 1 1533-4880/2016/16/040/018 doi:10.1166/jnn.2016.10885