IP: 193.32.95.246 On: Mon, 10 Dec 2018 00:24:35 Copyright: American Scientific Publishers Delivered by Ingenta Copyright © 2019 American Scientific Publishers All rights reserved Printed in the United States of America Review Journal of Nanoscience and Nanotechnology Vol. 19, 1889–1907, 2019 www.aspbs.com/jnn Toxicity Concerns of Therapeutic Nanomaterials Rubbel Singla, Chandni Sharma, Ashish K. Shukla, and Amitabha Acharya Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061 (H.P.), India; Academy of Scientific & Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061 (H.P.), India In the modern era, research on the synthesis of nanoparticles (NPs) has been growing exponentially. Due to their small size together with extra-ordinary physico-chemical properties, a variety of NPs i.e., metallic, carbon-based, fluorescent, and polymer-based have been exploited in different fields such as tissue engineering, drug delivery, and various other therapeutic applications. Instead of multi-disciplinary applications of NPs, research dealing with the toxicity concerns and influence of such materials, on the public health, plants and environment is still in its infancy. NPs can cause damage at the cellular, sub-cellular, molecular and protein levels owing to their extremely small size, large surface area to volume ratio, shape, and surface functionality. The present review is aimed to provide wide-ranging information related to NPs toxicology, the mechanisms of action, routes of their entry into the body and probable impacts on human health. Understanding of NPs entry routes into the body entails further research so as to update policymakers and regulatory bodies about the toxicity concerns associated with these nanomaterials. Proper characterization of NPs, factors affecting uptake and toxicity of NPs, as well as an understanding of processes when NPs come in contact with living beings, is critical to estimate the possible hazards. Keywords: Metallic Nanoparticles, Polymeric Nanoparticles, Carbon Nanomaterials, Toxicity, Routes of Administration. CONTENTS 1. Introduction ........................................ 1889 2. Toxicity of Metallic Nanoparticles ....................... 1890 2.1. Gold Nanoparticles (AuNPs) ....................... 1890 2.2. Silver Nanoparticles (AgNPs) ...................... 1891 2.3. Zinc Oxide Nanoparticles (ZnO NPs) ................ 1891 2.4. Titanium Dioxide Nanoparticles (TiO 2 NPs) ........... 1892 2.5. Copper Oxide Nanoparticles (CuO NPs) .............. 1892 2.6. Iron Oxide Nanoparticles (Fe 2 O 3 and Fe 3 O 4 NPs) ....... 1893 2.7. Other Metallic Nanoparticles ....................... 1893 3. Toxicity of Fluorescent Nanomaterials ................... 1894 4. Toxicity of Polymeric Nanoparticles ..................... 1895 4.1. Synthetic Polymeric Nanoparticles ................... 1895 4.2. Natural Polymeric Nanoparticles .................... 1896 5. Toxicity of Carbon-Based Nanomaterials .................. 1896 6. Toxicity of 2D Transition Metal Dichalcogenides (TMD) Nanoparticles ....................................... 1898 7. Routes of NPs Entry into the Body and Toxicity Mechanisms ........................................ 1901 8. Factors Affecting Toxic Behaviour of NPs ................ 1902 9. Concluding Remarks ................................. 1903 Acknowledgments ................................... 1903 References and Notes ................................ 1903 Author to whom correspondence should be addressed. 1. INTRODUCTION The development of nanotechnology and the formation of nanoparticles (NPs) have skyrocketed in the global world. NPs possess large surface area to volume ratio, small size and various other thermal and mechanical characteristics that facilitate their biological applicability different from their bulk counterparts. 1 When these bulk constituents are broken down into smaller particles, their properties and surface behaviour fluctuates abruptly which is responsi- ble for increasing the reactivity of NPs. 2 In the past few decades, the applicability of NPs has risen beyond a cer- tain limit in various biomedical applications such as drug delivery, diagnosis, therapy, and tissue engineering in the clinical medicine. 34 In-spite of thousand benefits of NPs, it is pre-requisite to look on the other side to investigate the potential adverse consequences of these NPs after their exposure to humans and the environment. 5 The use of several kinds of NPs is flourishing in therapeutics, those results in their rapid accumulation into the environment during synthesis, usage and waste removal. 6 Nano-toxicology, a new field came into origin only recently years after the various NPs had already been J. Nanosci. Nanotechnol. 2019, Vol. 19, No. 4 1533-4880/2019/19/1889/019 doi:10.1166/jnn.2019.16502 1889