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Nanotechnology in the Life Sciences
Necdet Saglam Feza Korkusuz Ram Prasad Editors
Nanotechnology Applications in Health and Environmental Sciences
Nanotechnology in the Life Sciences Series Editor Ram Prasad Department of Botany Mahatma Gandhi Central University Motihari, Bihar, India
Nano and biotechnology are two of the 21st century’s most promising technologies. Nanotechnology is demarcated as the design, development, and application of materials and devices whose least functional make up is on a nanometer scale (1 to 100 nm). Meanwhile, biotechnology deals with metabolic and other physiological developments of biological subjects including microorganisms. These microbial processes have opened up new opportunities to explore novel applications, for example, the biosynthesis of metal nanomaterials, with the implication that these two technologies (i.e., thus nanobiotechnology) can play a vital role in developing and executing many valuable tools in the study of life. Nanotechnology is very diverse, ranging from extensions of conventional device physics to completely new approaches based upon molecular self-assembly, from developing new materials with dimensions on the nanoscale, to investigating whether we can directly control matters on/in the atomic scale level. This idea entails its application to diverse fields of science such as plant biology, organic chemistry, agriculture, the food industry, and more. Nanobiotechnology offers a wide range of uses in medicine, agriculture, and the environment. Many diseases that do not have cures today may be cured by nanotechnology in the future. Use of nanotechnology in medical therapeutics needs adequate evaluation of its risk and safety factors. Scientists who are against the use of nanotechnology also agree that advancement in nanotechnology should continue because this field promises great benefits, but testing should be carried out to ensure its safety in people. It is possible that nanomedicine in the future will play a crucial role in the treatment of human and plant diseases, and also in the enhancement of normal human physiology and plant systems, respectively. If everything proceeds as expected, nanobiotechnology will, one day, become an inevitable part of our everyday life and will help save many lives. More information about this series at http://www.springer.com/series/15921
Necdet Saglam • Feza Korkusuz • Ram Prasad Editors
Nanotechnology Applications in Health and Environmental Sciences
Editors Necdet Saglam Department of Nanotechnology and Nanomedicine Graduate School of Science and Engineering Hacettepe University Ankara, Turkey
Feza Korkusuz Department of Sports Medicine Hacettepe University Faculty of Medicine Ankara, Turkey
Ram Prasad Department of Botany Mahatma Gandhi Central University Motihari, Bihar, India
ISSN 2523-8027 ISSN 2523-8035 (electronic) Nanotechnology in the Life Sciences ISBN 978-3-030-64409-3 ISBN 978-3-030-64410-9 (eBook) https://doi.org/10.1007/978-3-030-64410-9 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2021 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Preface
Nanoscience and nanotechnologies are leading to a major point in our understanding of nature. Nanotechnology can be basically defined as the creation and use of nano-sized systems, devices, and structures, which have special functions or properties because of their small size. This book entitled Nanotechnology Applications in Health and Environmental Sciences generally focuses on biotechnological and environmental applications of nanomaterials. It covers popular and various nanomedical topics such as oncology, genetics, and reconstructive medicine. Additionally, many chapters give leading information on nano-sensor applications and usage in recognized fields. Also, two novel subjects have been included by our colleagues: lantibiotics and microbiota. This book is useful for nanotechnologists, microbiologists, technocrats, policy makers, and researchers who are interested in nanomedicine and nano-biotechnology as well as environmental nanotechnology, so the reader is given detailed and updated knowledge in various nano applications from our esteemed authors. Each chapter is written by globally recognized academicians to provide an up-to-date and detailed account of our knowledge of nanobiotechnology and numerous applications in health and environmental sciences. We appreciate the many people who helped us to bring this book to light. We wish to thank Eric Stannard, Senior Editor, Botany, Springer, for his generous assistance, constant support, and patience in initializing the volume. The editors are very thankful to the Springer team, particularly Nicholas DiBenedetto, Anthony Dunlap, and Rahul Sharma (Project Coordinator), for the kind care and constant encouragement received. Ram Prasad would like to thank honorable vice chancellor Prof. Dr. Sanjeev Kumar Sharma, MGCU, Bihar, India, for his continuous support and inspirations in putting everything together. Special thanks are due to editor’s wellwishers, colleagues, and friends. Ankara, Turkey Necdet Saglam Ankara, Turkey Feza Korkusuz Motihari, Bihar, India Ram Prasad
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Contents
1 Diverse Manifolds of Biogenic Nanoparticles in Synthesis, Characterization, and Applications�������������������������������������������������������� 1 Jeyaraj Pandiarajan 2 Impact of Nanoparticles on Human Microbiota ���������������������������������� 29 Fadime Kiran 3 In Vitro Applications of Nanoparticles�������������������������������������������������� 41 Beste Cagdas Tunali, Dogan Tunali, and Mustafa Turk 4 Nanoparticles for Anticancer Drug Delivery���������������������������������������� 71 Eylem Güven 5 Green Synthesis of Iron Oxide Nanoparticles and Its Biomedical Applications ������������������������������������������������������������ 83 Mansee Thakur, Smital Poojary, and Niharika Swain 6 Nano-Forensics: The New Perspective in Precision Forensic Science���������������������������������������������������������������������� 111 Naresh Kumar and Arun Sharma 7 Recent Advances in Nanomaterial-Based Diagnosis and Treatment: Next-Generation Sequencing, Microarray and DNA Origami������������ 135 Celal Ulger, Esra Örenlili Yaylagül, Aykut Bilir, and Necdet Saglam 8 Nanobiosensors for Biomedical Applications���������������������������������������� 147 Yeşeren Saylan, Fatma Yılmaz, and Adil Denizli 9 Emerging Role of Nanomaterial-Assisted Biosensors for Circulating Tumor Cell Detection���������������������������������������������������� 159 Nura Brimo and Dilek Çökeliler Serdaroğlu 10 Advanced Functional Polymers for Biomedical Applications: Drug, Sensor, Diagnosis, and Prognosis ������������������������������������������������ 181 Kevser Kuşat and Sinan Akgöl vii
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11 SERS Sensor Applications in Environmental Analysis and Biotechnology�������������������������������������������������������������������� 197 Uğur Tamer, Hilal Torul, Üzeyir Doğan, Merve Eryılmaz, Ayşen Gümüştaş, İsmail Hakkı Boyacı, Sibel A. Özkan, and Bengi Uslu 12 Design and Creation of Micro/Nano Environment in Regenerative and Restorative Medicine�������������������������������������������� 237 Arda Kucukguven and Ibrahim Vargel 13 Presenting and Treating Bone Infections Using Silver Ion Containing Nano-hydroxyapatite ���������������������������������������� 257 Nusret Köse, Aydan Ayşe Köse, Ayşe Gül Toktaş, and Aydın Doğan 14 Trace Element Containing Nano-HAp for Preventing Musculoskeletal Infections���������������������������������������������������������������������� 269 Merve Gizer, Özge Boyacıoğlu, Petek Korkusuz, and Feza Korkusuz 15 Biotechnological Approaches in Maintenance of a Healthy Immune System for Protection Against Diseases�������������������� 291 Emin Umit Bagriacik 16 Production and Characterization of Antibiotic Containing Nano Calcium Phosphates�������������������������������������������������� 299 Feray Bakan 17 Lantibiotics Nanotechnology, Bioengineering, and Biotechnology ���� 319 Mesut Sam, Semran Saglam, Serap Altindag, Kazim Kose, Ezgi Emul, Lokman Uzun, and Necdet Saglam 18 Microbial Nanotechnology in Reference to Postmortem Diagnosis���� 333 Mahmut Şerif Yıldırım, Ramazan Akçan, Michal Kaliszan, and Necdet Saglam 19 Cleanup and Pollution with Nanoparticles: Environmental Dilemma ������������������������������������������������������������������������ 347 Feride Öykü Sefiloğlu and Işıl Akmehmet Balcıoğlu 20 Environmental Mycobiotechnology in Special Reference to Fungal Bioremediation������������������������������������������������������ 361 Ozlem Abaci Gunyar and Alev Haliki Uztan 21 Nanoinsecticides: Preparation, Application, and Mode of Action������ 385 Fatemeh Graily-Moradi and Behnam Asgari Lajayer 22 Design and Analysis of Induction-Balance Sensor Using Non-spiral Planar Microcoils for Biomedical Applications������������������������������������ 405 S. Krishnapriya, Rama S. Komaragiri, and K. J. Suja Index������������������������������������������������������������������������������������������������������������������ 423
About the Editors
Feza Korkusuz graduated from Medical Faculty, Ankara University, Ankara, Turkey, in 1986. He attended specification in Orthopedic Surgery in Traumatology at the Department of Orthopedic Surgery and Traumatology, Medical Faculty, Gazi University. Between 1989 and 1990, he studied at the Department of Orthopaedic Surgery, Faculty of Medicine, Osaka University, Japan, and he graduated from Osaka University with a postgraduate diploma. His clinical and research studies focused on Spine Surgery, Sports Medicine, and Basic Research. He has worked at Middle East Technical University, Ankara, Turkey, for 20 years as an orthopedic surgeon at the Medical Center as the Director and Head of Department of Physical Education and Sports. In 1994 and in 2001 he became an Associate Professor and Professor, respectively. In the year 2000, he received the Scientific and Technological Research Council of Turkey Promotion Award in Medical Sciences. Between 1991 and 2016, he was a member of the Orthopaedic Research Society. In 2008, he became an active member of the Association of Bone and Joint Surgeons, and since 2006, he has been a member of the corresponding and deputy editor of Clinical Orthopaedics and Related Research. Since 2017, he has become an active member of the Turkish Academy of Sciences and has worked as a vice president in the Scientific and Technological Research Council of Turkey (TUBITAK).
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Ram Prasad is associated with the Department of Botany, Mahatma Gandhi Central University, Motihari, Bihar, India. His research interest includes applied and environmental microbiology, plant–microbe interactions, sustainable agriculture, and nanobiotechnology. Dr. Prasad has more than two hundred publications to his credit, including research papers, review articles and book chapters and five patents issued or pending, and edited or authored several books. Dr. Prasad has twelve years of teaching experience and has been awarded the Young Scientist Award and Prof. J.S. Datta Munshi Gold Medal by the International Society for Ecological Communications; FSAB fellowship by the Society for Applied Biotechnology; the American Cancer Society UICC International Fellowship for Beginning Investigators, USA; Outstanding Scientist Award in the field of Microbiology by Venus International Foundation; BRICPL Science Investigator Award and Research Excellence Award, etc. He has been serving as editorial board members of Frontiers in Microbiology, Frontiers in Nutrition, Archives of Phytopathology and Plant Protection, Phyton-International Journal of Experimental Botany, Journal of Renewable Materials, IET Nanobiotechnology, and Biocell; and serves as series editor of Nanotechnology in the Life Sciences, Springer Nature, USA. Previously, Dr. Prasad served as Assistant Professor at Amity University Uttar Pradesh, India; Visiting Assistant Professor at Whiting School of Engineering, Department of Mechanical Engineering at Johns Hopkins University, Baltimore, United States, and Research Associate Professor at the School of Environmental Science and Engineering, Sun Yat-sen University, Guangzhou, China. Necdet Saglam graduated from the Faculty of Science, Department of Biology, Hacettepe University, Ankara, Turkey. Between 1991 and 2010, he worked as an Associated Professor and Professor in the Faculty of Education, Department of Biology, Hacettepe University. During the years between 2007 and 2011, he has become Rector of Aksaray University, Aksaray, Turkey. He has worked as a Professor for 10 years in the Division of Nanotechnology and Nanomedicine, Graduate School of Science and Engineering, Hacettepe University, Ankara, Turkey. He has joined a number of academic committees and served as chair, editor, and referee. He was Vice Dean of Education Faculty, Hacettepe University, from 1997 to 2006. He has supervised a number of graduate theses on science education and any other fields science. At present, he teaches Nanotechnology, Nanomedicine, Biotechnology, Microbiology, and Genetics and in these subject areas, he has been part of several research project teams. He has published many articles and chapters in esteemed journals and books and also presented papers at international conferences.
Contributors
Ramazan Akçan Department of Forensic Medicine, Medical Faculty, Hacettepe University, Ankara, Turkey Sinan Akgöl Department of Biochemistry, Ege University, İzmir, Turkey Serap Altindag Aksaray University, Graduate School of Science, Aksaray, Turkey Emin Umit Bagriacik Department of Immunology, Gazi University, Medical School, Ankara, Turkey Gazi University Lifesciences Research Center, Ankara, Turkey Feray Bakan SUNUM Sabancı University Nanotechnology Research and Application Center, Istanbul, Turkey Işıl Akmehmet Balcıoğlu Institute of Environmental Sciences, Boğaziçi University, Istanbul, Turkey Aykut Bilir Graduate School of Science and Engineering, Nanotechnology and Nanomedicine Division, Hacettepe University, Ankara, Turkey İsmail Hakkı Boyacı Department of Food Engineering, Hacettepe University, Ankara, Turkey Özge Boyacıoğlu Department of Bioengineering, Graduate School of Science and Engineering, Hacettepe University, Ankara, Turkey Basic Sciences Division, Department of Medical Biochemistry, Faculty of Medicine, Atılım University, Ankara, Turkey Nura Brimo Biomedical Engineering Department, Başkent University, Ankara, Turkey Adil Denizli Department of Chemistry, Hacettepe University, Ankara, Turkey
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Aydın Doğan Department of Materials Science and Engineering, Eskişehir Technical University, Eskisehir, Turkey Üzeyir Doğan Faculty of Pharmacy, Department of Analytical Chemistry, Gazi University, Ankara, Turkey Ezgi Emul Graduate School of Science and Engineering, Nanotechnology and Nanomedicine Division, Hacettepe University, Ankara, Turkey Merve Eryılmaz Faculty of Pharmacy, Department of Analytical Chemistry, Gazi University, Ankara, Turkey Merve Gizer Department of Stem Cell Sciences, Graduate School of Health Sciences, Hacettepe University, Ankara, Turkey Fatemeh Graily-Moradi Faculty of Agriculture, Department of Plant Protection, University of Tabriz, Tabriz, Iran Ayşen Gümüştaş Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara, Turkey Faculty of Pharmacy, Department of Pharmaceutical Microbiology, Ankara University, Ankara, Turkey Ozlem Abaci Gunyar Faculty of Science, Department of Biology, Basic and Industrial Microbiology Section, Ege University, Izmir, Turkey Eylem Güven Nanotechnology and Nanomedicine Division, Hacettepe University, Ankara, Turkey Michal Kaliszan Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland Fadime Kiran Faculty of Science, Department of Biology, Pharmabiotic Technologies Research Laboratory, Ankara University, Ankara, Turkey Rama S. Komaragiri Department of Electronics and Communication, Bennett University, Noida, India Feza Korkusuz Department of Sports Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey Petek Korkusuz Department of Histology and Embryology, Faculty of Medicine, Hacettepe University, Ankara, Turkey Aydan Ayşe Köse Department of Plastic and Reconstructive Surgery, Eskişehir Osmangazi University, Eskisehir, Turkey Kazim Kose Faculty of Science and Arts, Department of Chemistry, Hitit University, Çorum, Turkey Nusret Köse Department of Orthopedics and Traumatology, Eskişehir Osmangazi University, Eskisehir, Turkey
Contributors
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S. Krishnapriya Department of Electronics and Communication, MITS, Varikoli, Kerala, India Arda Kucukguven Faculty of Medicine, Department of Plastic Reconstructive and Aesthetic Surgery, Hacettepe University, Ankara, Turkey Naresh Kumar DNA Division, Regional Forensic Science Laboratory, Central Range, Mandi, Himachal Pradesh, India Kevser Kuşat Turkish Health of Ministry, Turkish Medicines and Medical Devices Agency, Ankara, Turkey Behnam Asgari Lajayer Faculty of Agriculture, Department of Soil Science, University of Tabriz, Tabriz, Iran Sibel A. Özkan Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara, Turkey Faculty of Pharmacy, Department of Pharmaceutical Microbiology, Ankara University, Ankara, Turkey Jeyaraj Pandiarajan Department of Biotechnology, Ayya Nadar Janaki Ammal College, Sivakasi, Tamil Nadu, India Smital Poojary Department of Medical Biotechnology, MGM School of Biomedical Sciences, MGM Institute of Health Sciences, Navi Mumbai, India Necdet Saglam Graduate School of Science and Engineering, Nanotechnology and Nanomedicine Division, Hacettepe University, Ankara, Turkey Semran Saglam Department of Physics, Gazi University, Ankara, Turkey Mesut Sam Faculty of Science and Letters, Department of Biology, Aksaray University, Aksaray, Turkey Yeşeren Saylan Department of Chemistry, Hacettepe University, Ankara, Turkey Feride Öykü Sefiloğlu Institute of Environmental Sciences, Boğaziçi University, Istanbul, Turkey Dilek Çökeliler Serdaroğlu Biomedical Engineering Department, Başkent University, Ankara, Turkey Arun Sharma Directorate of Forensics Services, Shimla, Himachal Pradesh, India K. J. Suja Department of Electronics and Communication, NIT Calicut, Kattangal, Kerala, India Niharika Swain Department of Oral Pathology, MGM Dental College and Hospital, Medical Genetics, MGM Institute of Health Sciences, Navi Mumbai, India Uğur Tamer Faculty of Pharmacy, Department of Analytical Chemistry, Gazi University, Ankara, Turkey
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Mansee Thakur Department of Medical Biotechnology, MGM School of Biomedical Sciences, MGM Institute of Health Sciences, Navi Mumbai, India Ayşe Gül Toktaş Department of Materials Science and Engineering, Eskişehir Technical University, Eskisehir, Turkey Hilal Torul Faculty of Pharmacy, Department of Analytical Chemistry, Gazi University, Ankara, Turkey Beste Çağdaş Tunalı Engineering Faculty, Bioengineering Department, Kırıkkale Universıty, Kırıkkale, Turkey Doğan Tunalı Engineering Faculty, Bioengineering Department, Kırıkkale Universıty, Kırıkkale, Turkey Mustafa Türk Engineering Faculty, Bioengineering Department, Kırıkkale Universıty, Kırıkkale, Turkey Celal Ülger Faculty of Arts and Science, Department of Biology, Molecular Biology, Aydın Adnan Menderes University, Aydın, Turkey Bengi Uslu Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara, Turkey Faculty of Pharmacy, Department of Pharmaceutical Microbiology, Ankara University, Ankara, Turkey Alev Haliki Uztan Faculty of Science, Department of Biology, Basic and Industrial Microbiology Section, Ege University, Izmir, Turkey Lokman Uzun Faculty of Science, Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara, Turkey Ibrahim Vargel Faculty of Medicine, Department of Plastic Reconstructive and Aesthetic Surgery, Hacettepe University, Ankara, Turkey Esra Örenlili Yaylagül Faculty of Health Sciences, Department of Nutrition and Dietetics, Aydın Adnan Menderes University, Aydın, Turkey Mahmut Şerif Yıldırım Department of Forensic Medicine, Medical Faculty, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey Fatma Yılmaz Department of Chemistry Technology, Abant Izzet Baysal University, Bolu, Turkey
Chapter 1
Diverse Manifolds of Biogenic Nanoparticles in Synthesis, Characterization, and Applications Jeyaraj Pandiarajan
Contents 1.1 I ntroduction: Nanotechnology and Nanoparticles 1.2 Nanofabrication of Metals 1.2.1 Synthesis of Metallic Nanoparticles 1.3 Types of Nanoparticles 1.3.1 Silver Nanoparticles 1.3.2 Gold Nanoparticles 1.3.3 Magnetic Nanoparticles 1.3.4 Platinum Nanoparticles 1.4 Paradigms of Metallic Nanoparticles 1.4.1 Properties and Features of Metallic Nanoparticles 1.5 Methods of Nanosynthesis 1.5.1 Chemical Reduction 1.5.2 Physical Methods 1.5.3 Biological Synthesis 1.6 Characterization of Nanoparticles 1.6.1 Particle Size Analysis 1.6.2 X-Ray Diffraction (XRD) 1.6.3 Dynamic Light Scattering (DLS) 1.6.4 Scanning Electron Microscopy 1.6.5 TEM 1.6.6 Atomic Force Microscopy (AFM) 1.7 Application of Nanotechnology 1.7.1 Bacterial Detection 1.7.2 Protein Purification 1.8 Conclusion References
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J. Pandiarajan (*) Department of Biotechnology, Ayya Nadar Janaki Ammal College, Sivakasi, Tamil Nadu, India e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2021 N. Saglam et al. (eds.), Nanotechnology Applications in Health and Environmental Sciences, Nanotechnology in the Life Sciences, https://doi.org/10.1007/978-3-030-64410-9_1
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1.1 Introduction: Nanotechnology and Nanoparticles Nanoscience is the study of ultra-small structures, materials and devices. In recently, nanoscience has been established as a new interdisciplinary science in the field of biological sciences. It can be entered in different range of applied sciences such as chemistry, physics, life sciences, medical science, and engineering. Targeted research and development for understand to manipulate and measure at the materials with atomic, molecular, and super molecules dimensions (Mourato et al. 2011). The word “nano” is used to indicate one billionth of meter or 10−9 (Li et al. 2011a, b). Nano, a scientific term used for determining the size of particle (Albrecht et al. 2006). The term Nanotechnology was coined by Professor Norio Taniguchi of Tokyo Science University in the year 1974. Nanotechnology is a swiftly mounting multibillion-dollar industry, with research being closely supported by governments, and particularly the US. Nanoscale materials are previously built-in hooked on more than 580 consumer products viz food, packaging, cosmetics, clothing, and paint (Paull and Lyons 2008). Nanotechnology is the design, characterization, production and application of structures, devices and systems by controlling shape and size at the nanoscale. It involves the production, manipulation and use of materials ranging in size from less than a micron to that of individual atoms from not only chemical approaches but also biological materials. Nanotechnology is a rapidly expanding and potentially beneficial field with tremendous implications for society, industry, and medicine (Mondal et al. 2011). Nanobiotechnology is a branch of nanotechnology, developed due to the incredible development in both biotechnology and nanotechnology. It is a multidisciplinary field involving research and development of technology in different fields of science like biotechnology, nanotechnology, physics, chemistry and material science. It deals with biofabrication of nano-objects of bifunctional macromolecules usable as tools to construct or manipulate nano-objects (Rai et al. 2009). Since, microbial cells offer many advantages like physiological diversity, small size, genetic manipulability, and controlled cultivability; they are thus regarded for the synthesis of diversity of nanostructures materials and instruments for nanosciences. This rapidly developing field of nanoscience has raised the possibility of using therapeutic nanoparticles in the diagnosis and treatment of human cancers (Yezheyev et al. 2006). The nanotechnology is presently one of the pivotal focuses of Science, Technology, and Innovation activities in all mechanized countries. The hoards in the area have been mounting and achieved global five billion dollars in 2002. There are estimates that from 2010 to 2015, the global souk for industrial materials, products and processes based on nanotechnology will be of one trillion dollars. This huge production will be dispersed over almost all financial side sectors, since the nanotechnology will affect an immense shape of industrial products and processes, in all areas, in addition creating novel overhaul activities (Dos Anjos et al. 2014). Nanomaterials are materials possessing grain sizes on the order of a billionth of a meter. They manifest extremely fascinating and useful properties. It can be exploited for a variety of structural and non-structural applications. A
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nanocrystalline material has grains on the order of 1–100 nm (Zhang and Webster 2009). Some of the applications of nanomaterials to biology or medicine or agriculture are fluorescent biological labels, drug and gene delivery, biodetection of pathogens, biosciences, detection of proteins, probing of DNA structure, tissue engineering, tumor destruction via heating (hyperthermia), separation, and purification of biological molecules and cells (Prasad et al. 2014, 2016, 2017). Nanoparticles are fundamental building blocks of nanotechnology. In the last decade, nanoparticles have been gaining a booming scientific interest due to their unique electronic, optical, mechanical, magnetic, and chemical properties that are scientifically from those of bulk materials. Metal nanoparticles have a high specific surface area and a high fraction of surface atoms have been studied extensively because of their unique physicochemical characteristics including catalytic activity, optical properties, electronic properties, antibacterial properties, and magnetic properties. (Kreuter 2007; Prasad et al. 2016). In contemporary years, we have witnessed extraordinary growth of research and applications in the blooming sector of nanoscience and nanotechnology. There is increasing hopefulness that nanotechnology, as applied to medicine, will bring noteworthy advances in the diagnosis and treatment of disease. Predictable applications in medicine comprising drug delivery, both in vitro and in vivo diagnostics, nutraceuticals, and production of improved biocompatible materials (De Jong et al. 2005). Engineered nanoparticles are an imperative means to realize a number of these applications. It has to be familiar that not all particles used for medical purposes fulfill to the recently expected and now generally accepted definition of a size ≤100 nm. On the other hand, this does not necessarily have a crash on their functionality in medical applications. The basis why these nanoparticles (NPs) are eye- catching for therapeutic purposes is based on their important and unique features, such as their surface-to-mass ratio that is much larger than that of other particles, their discrete amount of properties and their ability to adsorb and carry other compounds. NPs have a comparatively huge (functional) surface which is able to attach, adsorb and carry other compounds such as drugs, probes, and proteins. However, many challenges must be overcome if the application of nanotechnology is to realize the projected understanding of the pathophysiological basis of disease, bring more state-of-the-art diagnostic opportunities, and yield enhanced therapies. Although the definition identifies nanoparticles as having dimensions below 0.1μm or 100 nm, particularly in the area of drug delivery relatively large (size >100 nm) nanoparticles may be desirable for loading an adequate sum of drug onto the particles. In addition, for drug delivery not only engineered particles may be used as carrier, but also the drug itself may be formulated at a nanoscale, and then function as its own “carrier” (Cascone et al. 2002). The work of art of the engineered nanoparticles may vary. Foundation materials may be of biological origin like phospholipids, chitosan, lipids, lactic acid, dextran, or have more “chemical” characteristics like various polymers, carbon, silica, and metals. Their contact with cells for some of the biological components like phospholipids will be quite diverse compared to the nonbiological components such as metals like iron or cadmium. Particularly in
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the area of engineered nanoparticles of polymer origin there is an enormous area of potential for the chemical composition. On the other hand, model studies to the performance of nanoparticles have largely been investigated with nondegradable particles. Most data concerning the biological behavior and toxicity of particles comes from studies on inhaled nanoparticles as part of the inadvertent release of ultrafine or nanoparticles by combustion- derived processes such as diesel exhaust particles (Oberdörster et al. 2005). Several studies have clearly demonstrated that contact to these combustions derived ultrafine particles/nanoparticles is linked with a wide variety of effects including pulmonary inflammation, immune adjuvant effects (Granum and Lovik 2002), and systemic effects including blood coagulation and cardiovascular effects (Oberdörster et al. 2005). Since the cut-off size for both ultrafine and nanoparticles (100 nm) is the same, now both terms are used as equivalent. Based on the adverse effects of ultrafine particles as part of environmental pollution, engineered nanoparticles may be suspected of having similar adverse effects.
1.2 Nanofabrication of Metals 1.2.1 Synthesis of Metallic Nanoparticles There are two alternative approaches for synthesis of metallic nanoparticles. They are bottom-up approach and top-down approach. Bottom-up approach refers to the construction of structure atom-by-atom, molecule-by-molecule, or cluster-by- cluster. A distinct advantage of this approach is the enhanced possibility of obtaining metallic nanoparticles with comparatively lesser defects and more homogeneous chemical compositions. Examples for bottom-up approach are seeded growth method, polyol synthesis method, electrochemical, chemical reduction, and biological entities for fabrication of nanoparticles (Levins and Schafmeister 2006). In top-down approach, a suitable starting material is reduced in size using physical and chemical means. Physical methods of top down process are electric arc-discharge, laser ablation, physical vapor deposition, ion implantation, electric arc deposition, and ball milling (Pease and Chou 2008). The main advantage of physical method is they do not involve toxic chemicals and they are usually fast (Ghorbani et al. 2011). The classified nanotechnologies into wet and dry nanotechnology, the first one describes the living biosystems and the second one deals with man-made objects at nanoscale structures (Prasad et al. 2018a).
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1.2.1.1 Bacteria-Mediated Nanoparticle Synthesis Bacteria are known to produce inorganic materials either intracellular or extracellular. This makes them potential biofactories for the synthesis of nanoparticles like gold and silver. Silver is well known for its biocidal properties; however, some bacteria are known to be silver resistant reported by Slawson et al. (1992) and can accumulate silver on the cell wall to as much as 25% of their dry weight biomass, thus suggesting their use in industrial recovery of silver from ore materials (Pooley 1982). Klaus et al. (1999) reported that therefore, the use of prokaryotic bacteria as nanofactories was first studied. First noble metal nanoparticle synthesis, using bacteria, was done using silver resistant bacterial strains Pseudomonas stutzeri AG259, which were cultured in high concentrations of silver nitrates. It was demonstrated that the cells accumulate silver in large quantities and the majority of the silver was deposited in the form of particles of 200 nm of diameter. Samadi et al. (2009) showed the significant results were observed when bacteria Proteus mirabilis PTCC 1710 were used for producing silver nanoparticles. It was found that depending on the type of “broth” used during the incubation of bacteria, extracellular or intracellular synthesis can be promoted. This kind of selection makes bacteria-based green synthesis flexible, inexpensive, and a suitable method for large-scale production. It is important to point out that bacteria continued to grow after the synthesis of silver nanoparticles. However, the main drawback of using bacteria as nanofactories is the slow synthesis rate and the limited number of sizes and shapes available compared to the conventional chemical methods of synthesis. 1.2.1.2 Fungal-Mediated Nanoparticle Synthesis Similar to bacteria, due to their tolerance and metal bioaccumulation ability, high binding capacity, and intracellular uptake, fungi have been of interest in biological production of the metallic nanoparticles (Murali et al. 2003). Compared to bacteria, fungi are simpler to handle in a laboratory process. The mechanism of nanoparticle production using fungi is different; fungi secrete large amounts of enzymes which are used to reduce silver ions that induce the formation of the metal nanoparticles (Mandal et al. 2006; Prasad 2016). The first synthesis involving fungus-mediated approaches for the metal nanoparticle synthesis was performed in the beginning of the twentieth century, and silver nanoparticles (AgNPs) with diameter of nanometer were synthesized using fungus Verticillium (Ahmad et al. 2003a, b). In preceding investigations involving bacteria, bacteria Pseudomonas stutzeri AG259 isolated from silver mines were able to produce AgNPs of well-defined size and distinct morphology within the periplasmic space of the bacteria. Synthesis using Verticillium takes the green approach even further. During the exposure of the fungus to AgNO3 solution, the reduction of ions and the formation of AgNPs take place. Nanoparticles were approximately 25 nm in diameter presenting a rather good monodispersity and
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spherical morphology. Contrary to bacteria, AgNPs were formed below the surface of the fungal cells (Mukherjee et al. 2001). This result differs from the work of Klaus et al. (1999), where particle morphologies synthesized using bacteria ranged from spherical, triangular, to hexagonal. Mukherjee et al. (2001) reported that the mechanism of nanoparticle formation was then studied and the main hypothesis is that, in the case of fungi-based synthesis, the NPs are formed on the surface of the mycelia and not in the solution. It was then suggested that in the first step Ag+ ions are adsorbed on the surface of the fungal cells due to electrostatic interaction between negatively charged carboxylate groups in enzymes present in the cell wall of mycelia and positively charged Ag ions. Finally, the silver ions are then reduced by the enzymes present in cell wall, leading to the formation of silver nuclei. The shift from bacteria to fungi as a means of developing natural nanofactories offers the advantages of simpler downstream processing and handling of the biomass. Compared to bacteria, fungi are known to secrete much higher amounts of proteins, which tends to significantly increase the productivity of this biosynthetic approach; moreover, fungi could be used for the production of large amounts of metal nanoparticles (Prasad 2017; Prasad et al. 2018b). The first report involving extracellular synthesis of silver nanoparticles using eukaryotic systems such as fungi was reported by Ahmad et al. (2003a, b). They showed that secreted enzymes are responsible in the reduction process. Before this report, all the fungi-based biosyntheses were intracellular. Extracellular synthesis is advantageous as the synthesized nanoparticles will not bind to the biomass reported by Balaji et al. (2009) and Durán et al. (2005) and it is therefore possible to extend this approach for the biosynthesis of nanomaterials over a range of chemical compositions, such as oxides, nitrides, and so forth. When compared to other classes of microorganisms, their ecofriendliness and simplicity during handling lead to increasing the use of fungi in green synthesis (Abdel-Aziz et al. 2018). For example, fungus like white rot fungus is nonpathogenic and this contributes to the mass production of AgNPs done by Vigneshwaran et al. (2006). Another important factor for choosing the method of synthesis is the reaction rate. First report of rapid synthesis using fungi was using Aspergillus fumigatus that allowed obtaining monodispersed AgNPs within 10 min (Bhainsa and D’Souza 2006). In addition, one of the most common molds Aspergillus fumigatus was used to make AgNPs in a matter of minutes, when silver ions entered into contact with the cell filtrate. These investigations were clear examples describing suitability and the potential of using fungi for mass production of nanoparticles. More recently, AgNPs were synthesized using a Flavus fungus to be combined with antibiotics to enhance the biocidal efficiency against multidrug-resistant bacteria. This study demonstrated the efficiency of antibiotics combined with AgNPs (Naqvi et al. 2013). Similar to fungi, yeasts were also widely investigated for silver nanoparticle synthesis reported by Mourato et al. (2011). Silver-tolerant yeast strain MKY3 was first used for extracellular synthesis. The outcome of the synthesis was satisfying due to simplicity of the separation of the nanoparticles when using differential thawing done by Kowshik et al. (2003). After that, several studies followed
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but until recently synthesis has never been carried out by commercial baker’s yeast available in grocery stores. All the aggravating steps of cultivation of the yeast were avoided, thus making the process much simpler (Saravanan et al. 2014). Similar to moving from prokaryotes to eukaryotes green synthesis, the utilization of eukaryotic autotrophs widened the possibilities of green synthesis. For example, using marine algae Sargassum wightii allowed obtaining very stable nanoparticles compared to other biological methods (Singaravelu et al. 2007). Samuel et al. (2018) isolated three distinguished marine fungal isolates Aspergillus niger, A. michelle, and A. japonicus from south west coast of Tamilnadu. The marine sediment samples were collected by Hand core pushing technique. All the isolates were subjected to nanoparticle production. The production results had revealed that the nanoparticles are varying in size. Uniquely the nanoparticles formed by A. japonicus were measured about ~100 nm. The cytotoxic activity was revealed by MTT assay on MCF7 cell lines. There was 100% cell inhibition when concentration of the AgNPs reached 25, 50, and 100μg, respectively in the test solution. Notably, the IC50 value was found to be very lowest for the nanoparticles produced by A. japonicus and the value was found to be 1.47μg/ml. 1.2.1.3 Green Synthesis Using Plants Parashar et al. (2009) explained that nanoparticles derived from biological sources are environmentally benign and compatibility for pharmaceutical and other biomedical applications as they do not use toxic chemicals for the synthesis protocol. Mubarak Ali et al. (2011) reported the biological reduction of silver and gold nanoparticles by Mentha piperita leaf extract. Silver and gold nanoparticles were synthesized in ambient conditions and characterization of synthesized nanoparticles was carried out by UV–vis spectroscopy, FTIR, and SEM equipped with EDS. It is believed that phytochemicals present in the extract of M. piperita has reduced the silver and gold ions into metallic nanoparticles. This may be a first report that leaf had been sterilized before the extraction, we assumed to decant surface inhabitant microorganisms. The synthesized silver and gold exhibited a strong antibacterial activity against both E. coli and S. aureus. The process for the synthesis of nanoparticles in large scale using these readily available plant extract may have commercial viability and to develop studies in the interface between biology and material science. By using such plant extracts to develop nanomedicine against various human and veterinary pathogens. One of the first approaches of using plants as a source for the synthesis of metallic nanoparticles was with alfalfa sprouts (Gardea-Torresdey et al. 2003), which was the first report on the formation of AgNPs using a living plant system. Alfalfa roots have the capability of absorbing Ag from agar medium and transferring them into the shoots of the plant in the same oxidation state. In the shoots, these Ag atoms arranged themselves to form nanoparticles by joining themselves and forming larger arrangements.
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In comparison to bacteria and fungi, green synthesis using plants appears to be faster and the first investigations demonstrate that synthesis procedures are able to produce quite rapidly AgNPs. Shankar et al. (2003) showed that using Geranium leaf takes around 9 h reaching 90% reaction compared to the 24–124 h necessary for other reactions. Therefore, the use of plant extracts in green synthesis has spurred numerous investigations and studies up till now. It was demonstrated that the production of metal nanoparticles using plant extracts could be completed in the metal salt solution within minutes at room temperature, depending on the nature of the plant extract. After the choice of the plant extract, the main affecting parameters are the concentration of the extract, the metal salt, the temperature, the pH, and the contact time reported by Mittal et al. (2013a, b). In addition to the synthesis parameters, the main issue is the choice of the plant from which the extract could be used. The advantages of using plants for the synthesis of nanoparticles are that the plants are easily available and safe to handle and possess a large variety of active agents that can promote the reduction of silver ions. Most of the plant parts like leaves, roots, latex, bark, stem, and seeds are being used for nanoparticle synthesis (Kharissova et al. 2013; Prasad 2014). The most important point is the active agent contained in these parts which makes the reduction and stabilization possible. Ecofriendly plant extracts contain biomolecules, which act as both reducing and capping agents that form stable and shape-controlled nanoparticles. Main compounds which affect the reduction and the capping of the nanoparticles are biomolecules such as phenolics, terpenoids, polysaccharides, flavones, alkaloids, proteins, enzymes, amino acids, and alcoholic compounds. However, quinol and chlorophyll pigments, linalool, methyl chavicol, eugenol, caffeine, theophylline, ascorbic acid, and other vitamins have also been reported by Sharma et al. (2009). Ahmad et al. (2003a, b) reported that the nontoxic phytochemicals including aforementioned flavonoids and phenols have unique chemical power to reduce and also effectively wrap nanoparticles, thus preventing their agglomeration. Phenolic compounds possess hydroxyl and carboxyl groups, which are able to bind to metals. Most of the AgNPs synthesized through green synthesis are investigated for biomedicine and more particularly as antibacterial agent or for cancer treatment. Recent reports showed that it was possible using Acacia leucophloea extract (Murugan et al. 2014) to synthesize AgNPs of diameter ranging from 38–72 to 17–29 nm, respectively. The samples demonstrated very good antibacterial properties. In the same manner, Ganoderma neo-japonicum Imazeki was used for the synthesis of AgNPs as potential cytotoxic agents against breast cancer cells (Gurunathan et al. 2013). As these methods involving green chemistry are being more and more explored and scientists are starting to combine different options together, it was recently reported that the symbiotic biological systems such as Geranium leaf combined with endophytic fungus Colletotrichum sp. can synergize the outcome of the reaction. In fact, plants contain biomolecules which are able to stabilize unstable particles whereas fungi secrete enzymes for reduction (Shankar et al. 2003).
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1.3 Types of Nanoparticles 1.3.1 Silver Nanoparticles Nanoparticles of silver are between 1 and 100 nm in size. While frequently described as being “silver,” some are composed of a large percentage of silver oxide due to their large ratio of surface-to-bulk silver atoms. Numerous shapes of nanoparticles can be constructed depending on the application at hand. Commonly used are spherical silver nanoparticles but diamond, octagonal and thin sheets are also popular. Silver nanoparticles may eventually offer treatment of various diseases. In clinical, silver nanoparticles based wound dressings are perhaps the most universally used. There is also an effort to incorporate silver nanoparticles into a wide range of medical devices, including but not limited to bone cement, surgical instruments, and surgical masks. Hence, many people tried to synthesis AgNPs with a variety of synthesis methods including chemical reduction, electrochemical techniques, photochemical techniques, photochemical reactions, and now a day via green chemistry route. Use of plants and microbes in the synthesis of AgNPs is a quite novel method as it is cost effective and environmentally friendly and easily scaled up for large- scale synthesis (Christina et al. 2003).
1.3.2 Gold Nanoparticles The optical and electronic properties of gold nanoparticles are tunable by changing the size, shape, surface chemistry, or aggregation state. These unique optical- electronics properties have been researched and utilized in high technology applications such as organic photovoltaic, sensory probes, therapeutic agents, drug delivery in biological and medical applications, electronic conductors, and catalysis (Li et al. 2012). Sayed et al. (2005) reported that they are also useful in cancer imaging by selectively transporting gold nanoparticles into the cancer cell nucleus.
1.3.3 Magnetic Nanoparticles Marin et al. (2014) reported that magnetic nanoparticles can be manipulated using magnetic field gradients. Such particles commonly consist of magnetic elements such as iron, nickel, and cobalt and their chemical compounds. While nanoparticles are smaller than 1μm in diameter (typically 5–500 nm), the larger micro beads are 0.5–500μm in diameter. Magnetic nanoparticle clusters which are composed of a number of individual magnetic nanoparticles are known as magnetic nanobeads with a diameter of 50–200 nm.
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The physical and chemical properties of magnetic nanoparticles largely depend on the synthesis method and chemical structure. In most cases, the particles range from 1 to 100 nm in size and may display superparamagnetism (Lu et al. 2007; Abd- Elsalam et al. 2019). There are many applications for iron-oxide based nanoparticles in concert with magnetic resonance imaging (Colombo 2012). Magnetic CoPt nanoparticles are being used as an MRI contrast agent for transplanted neural stem cell detection (Xiaoting et al. 2011).
1.3.4 Platinum Nanoparticles Platinum nanoparticles are usually in the form of a suspension of submicrometer- size particles of platinum in a fluid, usually water. Colloid is technically defined as a stable dispersion of particles in a fluid medium (liquid or gas). Spherical platinumnanoparticles can be made with sizes between about 2 and 100 nm, depending on reaction conditions (Bigall et al. 2008). Platinum nanoparticles are suspended in the colloidal solution of brownish-red or black color. Nanoparticles come in wide variety of shapes including spheres, rods, cubes (Harris 1986), and tetrahedral (Ahmadi et al. 1996).
1.4 Paradigms of Metallic Nanoparticles 1.4.1 Properties and Features of Metallic Nanoparticles • The term metal nanoparticle is used to describe nanosized metals with dimensions (length, width, or thickness) within the size range 1–100 nm. • The existence of metallic nanoparticles in solution was first recognized by Faraday in 1857 and a quantitative explanation of their color was given by Mie in 1908. 1.4.1.1 The Main Characteristics of MNPs • Large surface-area-to-volume ratio as compared to the bulk equivalents; • Large surface energies; • The transition between molecular and metallic states providing specific electronic structure (local density of states LDOS); • Plasmon excitation; • Quantum confinement; • Short range ordering; • Increased number of kinks;
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• A large number of low-coordination sites such as corners and edges, having a large number of “dangling bonds” and consequently specific and chemical properties and the ability to store excess electrons. 1.4.1.2 Goals and Problems in Metallic Nanoparticles Synthesis • • • • • • • • • •
Ideally, metallic nanoparticles should be prepared by a method which: Is reproducible May control the shape of the particles Yields monodisperse metallic nanoparticles Is easy, cheap Use less toxic precursors: in water or more environmentally benign solvents (e.g., ethanol) Use the least number of reagents Use a reaction temperature close to room temperature With as few synthetic steps as possible (one-pot reaction) Minimizing the quantities of generated by-products and waste.
1.4.1.3 Risks of Synthetic Nanoparticles for Humans and Animals Let us first consider the risks posed by synthetic nanoparticles to human and animal health. In view of the route of entry of nanoparticles into the human or animal body, the available in vitro and in vivo studies give the following picture: • Nanoparticles have almost unlimited access to the body. They can enter the bloodstream through breathing (lungs) and via the digestive tract, and from there reach all the organs (liver, spleen, bone marrow, etc.). • It is unclear whether absorption can take place through the skin. This appears to be almost impossible for normal skin; but it is unclear what happens if the skin is damaged, for example by eczema. There are also indications that nanoparticles could pass via the skin into the lymphatic system and lymph nodes. • Under certain circumstances, some nanoparticles can cross the blood–brain barrier. • Nanoparticles can enter the brain directly via olfactory nerve fibers in the nasal mucosa. It is not known how they behave there. • Nanoparticles can penetrate cell membranes and reach the cell nucleus. Even if we do not know precisely how (insoluble) nanoparticles behave in the human body, the fact that they are capable of spreading throughout the body, interacting with cells and crossing the blood–brain barrier, is a further reason for care and caution when handling them (Limbach et al. 2007). Six clump, i.e., aggregate into botryoid agglomerates. This means that, above a cluster size of 1μm, their reactivity decreases. They are then also too large to enter the bloodstream via the lung. Toxic effects based on small size and high reactivity are then no longer
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significant. But in most cases, synthetic nanoparticles in particular are useful only if they do not clump. A special coating is added to the nanoparticles as an attempt to prevent clumping. This means that these particles remain reactive and highly mobile, and thus potentially toxic (even if toxicity is reduced by the coating). In vivo toxicological studies have so far been performed primarily in rats, mice, and fish. 1.4.1.4 T hese Studies Make It Clear That Synthetic Nanoparticles Are Potentially Severely Harmful • Various studies have shown that fullerenes and nanotubes, in particular, cause inflammation in the lungs if they are inhaled at a certain (high) dose. The substances such as gold, carbon black, and TiO2, 10 which are normally harmless but can be toxic in nanoscale form (Bottini et al. 2006). • The well-known—if not entirely undisputed—experiment by Eva Oberdörster using largemouth bass showed that the uptake of buckyballs in these fish caused severe brain damage within 48 h (Oberdörster 2005). • An earlier studies shows that the higher reactivity of nanoscale titanium dioxide can damage the microglia, which protect the central nervous system, through oxidative stress due to the formation of free radicals. • The results of a recent Chinese study (Chen et al. 2006) using nanoparticles of copper in mice included the following: “Nanoparticles induce gravely toxicological effects and heavy injuries on kidney, liver and spleen of experimental mice, but micro-copper particles do not, on mass basis.” In general, these particles are classified as class 3 (moderately toxic), in contrast to micro-copper, which is practically nontoxic. In addition, the toxicity is sex-dependent: male mice showed more severe toxic symptoms than females at the same particle mass. Naturally, there is a question of whether and how far these results can be transferred to humans. There are indications that extrapolation would be problematic, as the process of particle inhalation is different in rats than in humans and other large mammals: they appear to react more sensitively but have a more active immune system that breaks the particles down more quickly. In the few direct measurements undertaken in humans, however, it has been shown that certain risk groups, such as asthmatics, react more sensitively than healthy people to adventitious nanoparticles. Moreover, in vitro experiments with human cells suggest that synthetic nanoparticles, especially nanotubes and buckyballs, may severely harm human health. For example, it has been shown that a certain concentration of buckyballs causes 50% of human skin cells to die. Researchers at EMPA discovered in 2006 that nanotubes are especially harmful to lung cells when they clump together in a larger, needle-like form. Cell biologist Peter Wick says: “These agglomerates are similar to asbestos fibres—in both their appearance and their toxicity they appear, therefore, not to be completely harmless” (EMPA News 2/2006). Finally, it should be noted that even uncoated quantum
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dots can be toxic, i.e., can cause cell damage. This is because their core consists of toxic heavy metal compounds such as cadmium selenide. 1.4.1.5 T here Are Three Possible Ways in Which Bioactive Particles of This Kind Could Cause Cell Damage 1. By causing oxidative stress inside the cell or on its surface: “This means that free radicals form, i.e. molecules with a free electron, which are thus extremely reactive. The result is that the calcium level inside the cell rises, and the unwanted transcription of genes into proteins within the cell nucleus may be activated. Proteins can then cause tissue inflammation.” 2. Receptor molecules on the cell envelope are activated because metal atoms detach from the nanoparticles. The consequences would be the same as in case 1. 3. “The nanoparticle is swallowed whole by the cell and may enter the mitochondria, the ‘power houses’ of the cell. Their activity is disturbed by the presence of the particle.” Nanotechnology is an innovative field which influences all aspects of human’s life (Mohanpuria et al. 2008). The “green” method for nanoparticles synthesis which is rapidly traditional chemical synthesis is of great interest because of ecofriendliness, economic views, feasibility, and wide range of applications in several areas. Since the domain of biosynthesized nanoparticles is somewhat novel, and their use in different areas including the delivery of drug, cancer therapy, gene treatment and DNA analysis, antibacterial factors, biosensors, increasing response rates, separation science provided (Amin et al. 2015; Maddela et al. 2021). Generally, metal nanoparticles can be prepared and stabilized by chemical, physical and biological methods; the chemical approach, such as chemical reduction, electrochemical techniques, photochemical reduction and pyrolysis and physical methods, such as arc-discharge and physical vapor condensation (pvc) (Tavakoli et al. 2007) is used. Living organisms have huge potential for the production of nanoparticles/ nanodevices of wide applications (Mohanpuria et al. 2008).
1.5 Methods of Nanosynthesis 1.5.1 Chemical Reduction Typical reducing agents include polyols, NaBH4, N2H4, sodium citrate and N,N- dimethylformamide. Doubtless, in order to prevent aggregation of Ag NPs, it needs to stabilize with capping agents such as Sodium dodecyl sulphate (SDS), polyvinyl pyrrolidone (pvp), tri-sodium citrate (Jiang et al. 2006)
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1.5.1.1 Photochemical Method (Irradiation) Laser irradiation of an aqueous solution of Ag salt and surfactant can fabricate Ag NPs of well-defined shape and size distribution. No reducing agent is required in this method (Sharma et al. 2009). 1.5.1.2 Electrochemical Method (Electrolysis) Pyrolysis An appropriate amount of commercial reagent AgNO3 and Mg(NO3)2 was dissolved into deionized water to form an aqueous solution with a mass percentage of 40.0%, and molar ratio of AgNO3 and Mg(NO3)2 of 2:8. The solution was churned up and fed into nozzle with a solution feed rate of 500 mL/h, carrier gas flux of 0.30 MPa, and spray pyrolyzed in hot air of 790 °C. This was how the Ag/MgO composite powder was prepared. In order to remove MgO template from Ag/MgO composite powder, ammonium chloride (NH4Cl) solution was used. The MgO obtained from Mg(NO3)2 by spray pyrolysis was used as template to inhibit nano-Ag growth by separating nano-Ag grains from each other (Shi et al. 2008)
1.5.2 Physical Methods 1.5.2.1 Physical Vapor Condensation (PVC) In order to fabricate nanoparticles, the vaporization method has been frequently used, in which the target materials are vaporized by heat source and then rapidly condensed. The vaporization process can be subdivided into physical and chemical methods depending on whether the reaction is present. If the resultant nanoparticles have the same composition with the target materials, they are prepared by physical vapor condensation (PVC). However, nanoparticles having a different composition with the target are usually obtained by chemical vapor condensation (CVC), because the chemical reaction occurs between the vapor and other system components during the vaporization and condensation (Tavakoli et al. 2007). 1.5.2.2 Arc-Discharge Method A novel technique for preparing a nanosilver water suspension without surfactants and stabilizers was studied using the arc-discharge method. Silver wires (99.99%) 1 mm in diameter submerged in deionized water were used as electrodes. The DC arc-discharge system consists of five main parts: (1) two silver electrodes 1 mm in diameter, (2) a servo control system that maintains a constant distance between the
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electrodes, (3) a power supply system that controls the DC arc-discharge parameters, (4) a glass container with an electrode holder and deionized water to collect the silver colloids, (5) a stirring system with magnetic stirrer and stirring bar. In order to ionize the aqua medium between the electrodes, the DC arc-discharge system provides a pulse voltage of 70–100 V for 2–3 ms and then maintains a pulse of 20–40 V for around 10μs. During the arc-discharge, the surface layer of the Ag wires evaporates and condenses in the water. The transparent solution converts to a characteristic pale-yellow color and then a silver suspension is created (Tien et al. 2008). 1.5.2.3 Mechanical Ball Milling Mechanical milling as a solid state synthesis usually performed using ball milling equipments that generally divided to “low energy” and “high energy” category based on the value of induced the mechanical energy to the powder mixture (Boldyrev and Tkáčová 2000). Before a mechanical milling is started, powder(s) is loaded together with several heavy balls (steel or tungsten carbide) in a container. By vigorously shaking or high-speed rotation, a high mechanical energy is applied on the powders because of collision with heavy balls (Tavakoli et al. 2007).
1.5.3 Biological Synthesis 1.5.3.1 Metal Nanoparticles via Plants Plant extracts containing bioactive alkaloids, phenolic acids, polyphenols, proteins, sugars, and terpenoids are believed to have an important role in first reducing the metallic ions and stabilizing them (Marshall et al. 2007; Castro et al. 2011). The variation in composition and concentration of these active biomolecules between different plants and their subsequent interaction with aqueous metal ions is believed to be the main contributing factors to the diversity of nanoparticle sizes and shapes produced (Li et al. 2011a, b). The process begins by mixing a sample of plant extract with a metal salt solution. Biochemical reduction of the salts starts immediately and the formation of nanoparticles is indicated by a change in the color of the reaction mixture. During synthesis, there is an initial activation period when process metal ions are converted from their mono or divalent oxidation states to zerovalent states and nucleation of the reduced metal atoms takes place (Malik et al. 2014). This is immediately followed by a period of growth when smaller neighboring particles amalgamate to form larger nanoparticles that are thermodynamically more stable while further biological reduction of metal ions takes place. As growth progresses nanoparticles aggregate to form a variety of morphologies such as cubes, spheres, triangles, hexagons, pentagons, rods, and wires (Akhtar et al. 2013). In the final stage of synthesis, the plant extracts’ ability to stabilize the nanoparticle ultimately
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determines their most energetically favorable and stable morphology. Properties of the plants extract such as its concentration, metal salt concentration, reaction time, reaction solution pH, and temperature significantly influence the quality, size, and morphology of the synthesized nanoparticles (Mittal et al. 2013a, b and Dwivedi and Gopal 2010). 1.5.3.2 Microbial Routes for Nanoparticle Synthesis Biological strategies for dealing with high concentrations of metallic ions include changes in metal ion concentration via redox state changes, efflux systems, intracellular precipitation, and accumulation of metals, and extracellular formation of complexes (Dhillon et al. 2012; Srivastava et al. 2021). The major bacterial species used for the synthesis of metallic nanoparticles include Actinobacter sp., Escherichia coli, Klebsiella pneumonia, Lactobacillus spp., Bacillus cereus, Corynebacterium sp., and Pseudomonas sp. (Mohanpuria et al. 2008; Iravani 2014; Sunkar and Nachiyar 2012; Tollamadugu et al. 2011). Bacteria are known to synthesize metallic nanoparticles by either intracellular or extracellular mechanisms. For example, Ag nanoparticles have been synthesized using Pseudomonas stutzeriAG259 bacterium via a mechanism involving the NADH-dependent reductase enzyme that donates an electron and oxidizes to NAD+. The electron transfer results in the biological reduction of Ag ions to Ag nanoparticles (Ahmad et al. 2003a, b). Fungi are capable of producing mono dispersed nanoparticles and particle sizes over a wide range of different chemical compositions. Fungi possess some additional attributes when compared to their bacterial counterparts for the synthesis of metallic nanoparticles. For instance, fungi secrete large amounts of proteins and enzymes per unit of biomass, which results in larger amounts of nanoparticles being, manufactured (Ahmad et al. 2003a, b). Studies have shown that some fungi possess high intracellular metal uptake volumes and the synthesized particles tend to be smaller in size (Mukherjee et al. 2002). However, the culture conditions can have a significant influence during the biosynthesis of metallic nanoparticles. Extracellular and intracellular synthesis of nanoparticles using fungi has been investigated. In the case of intracellular synthesis, extraction procedures in downstream processing suffer from the drawback of low yields. In contrast, extracellular synthesis produces nanoparticles at the cell surface or at the periphery of the cell, which means they can be readily recovered in downstream processing (Dhillon et al. 2012; Kathiresan et al. 2009).
1.6 Characterization of Nanoparticles The particle size and size distribution of nanoparticles can be determined using numerous commercially available instruments. Instruments can be used for the analysis of dry powders and powders dispersed in suspension. In general, there are
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two basic methods of defining particle size. The first method is to inspect the particles and make actual measurements of their dimensions. Microscopic techniques, for example, measure many dimensional parameters from particle images. The second method utilizes the relationship between particle behavior and its size. This often implies an assumption of equivalent spherical size developed using a size- dependent property of the particle and relating it to a linear dimension [Ceramics and Glasses, 1991]. The different techniques used for characterization of nanomaterials, based on their different features, are described in the following sections. A rigorous but practical approach to reliable characterization of nanomaterials is essential for quality assurance and safe, rational development of nanomedicines and theranostics (Akhter et al. 2013). Nanoparticles are generally characterized by their size, morphology and surface charge, using such advanced microscopic techniques as scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The average particle diameter, their size distribution and charge affect the physical stability and the in vivo distribution of the nanoparticles. Electron microscopy techniques are very useful in ascertaining the overall shape of polymeric nanoparticles, which may determine their toxicity. The surface charge of the nanoparticles affects the physical stability and redispersibility of the polymer dispersion as well as their in vivo performance (Kim et al. 2013).
1.6.1 Particle Size Analysis Particle size distribution and morphology are the most important parameters of characterization of nanoparticles. Morphology and size are measured by electron microscopy. The major application of nanoparticles is in drug release and drug targeting. It has been found that particle size affects the drug release. Smaller particles offer larger surface area. As a result, most of the drug loaded onto them will be exposed to the particle surface leading to fast drug release. On the contrary, drugs slowly diffuse inside larger particles. As a drawback, smaller particles tend to aggregate during storage and transportation of nanoparticle dispersion. Hence, there is a compromise between a small size and maximum stability of nanoparticles (Redhead et al. 2001). 1.6.1.1 Surface Properties Many characteristics of nanomaterial interfaces are functions of atomic or molecular compositions of the surfaces and the physical surface structures that respond to the interactions of the nanomaterial with surrounding species. From the aspect of nanomedicine, these characteristics are considered the elements of surface properties in the environment of biological fluid. Among the different surface properties, surface composition, surface energy, wettability, surface charge, and species absorbance or adhesion are commonly considered important parameters (Patri et al. 2006).
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However, positively charged nanomaterials can be more toxic than their negatively charged counterparts. The positively charged amino-modified polystyrene-formulated NPs were cytotoxic to certain cell lines by inducing DNA damage (Liu et al. 2011). In contrast, the effects of surface charge on cytotoxicity and reactive oxygen species generation were enhanced in the negatively charged silica NPs of 20 nm in size, compared with those induced by silica NPs of the same size, but weaker negative charge (Park et al. 2013). Although the connection between increased cellular uptake of positively charged NPs and elevated cytotoxicity was typically demonstrated in in vitro studies, in vivo evidence is less convincing. The relation between surface charge/zeta potential and NP toxicity cannot be generalized (Luyts et al. 2013). 1.6.1.2 Stability Pharmaceutical stability refers to retaining the same properties for a period of time after the pharmaceutical is manufactured. Similar to conventional single-molecule pharmaceuticals, the stability of nanomedicines may be affected by one or more factors, such as temperature, moisture, solvents, pH, particle/molecular size, exposure to different types of ionizing and non-ionizing radiation, enzymatic degradation, and even the presence of other excipients and impurities (Patri et al. 2006). The stability of nanomaterial may impact its corresponding toxicity; for instance, a number of studies have shown that quantum dot cytotoxicity might be induced during synthesis, storage or even in vivo by oxidative or photolytic degradation of quantum dots (Hardman 2006).
1.6.2 X-Ray Diffraction (XRD) In a variety of X-ray spectroscopic modalities, XRD is a primary tool for completely resolving the tertiary structures of crystalline materials at the atomic scale. The diffraction of X-ray can be simply described as the reflection of a collimated beam of X-rays incident on the crystalline planes of an examined specimen according to Bragg’s law. Typically, XRD, based on wide-angle elastic scattering of X-rays, is a tool for characterizing crystalline size, shape and lattice distortion by long-range order, but is limited to disordered materials (Sapsford et al. 2011).
1.6.3 Dynamic Light Scattering (DLS) The principle of DLS is to monitor the temporal fluctuation of the elastic scattering intensity of light, i.e., Rayleigh scattering, induced from the Brownian motion of the particles/molecules of a size much smaller than the incident light wavelength, at a
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fixed scattering angle. The intensity fluctuation trace comprises a mixture of the constructive and destructive interferences of the scattered light, through which the particle size can be derived from analysis of the motion-dependent autocorrelation function using the Stokes–Einstein equation (Brar and Verma 2011 and Sapsford et al. 2011). Dynamic light scattering (DLS) is also called quasi-elastic light scattering (QELS) or photon correlation spectroscopy. This is one of the foremost techniques used to measure the radius of a particle in a medium. The motion of particles of micron or lower size is uncorrelated, i.e., they are random. As light scatters from such particles, there will be a shift in the phase of the scattered light which is random and as a result, when the scattered light rays from several particles are added together, constructive or destructive interference occurs. What we get is time- dependent fluctuation in the intensity of the scattered light. The scattering of light from particles undergoing Brownian motion also leads to a Doppler shift of the radiation, modifying the wavelength of the light. In a set-up, a laser light beam is sent through a sample containing particles. The sample has to be inhomogeneous in one of the several ways (such as due to the presence of particles, micelles, proteins, acoustic waves, etc.). The scattered light is received by a fast detector. If the intensity of the light is measured as a function of the scattered direction, we undertake what is called the static light scattering experiment. If the correlation of light intensity is measured as a function of time, we undertake a dynamic light scattering experiment (Pradeep 2007).
1.6.4 Scanning Electron Microscopy The first scanning electron microscope (SEM) debuted in 1938 (Von Ardenne) with the first commercial instruments around 1965. Its late development was due to the electronics involved in “scanning” the beam of electrons across the sample. Scanning electron microscopy (SEM) can provide a highly magnified image of the surface and the composition information of near surface regions of a material (Richard et al. 1992). The resolution of SEM can approach a few nanometers and the magnifications of SEM can be easily adjusted from about ten times to 300,000 times. In SEM, electron beam, accelerated by a relatively low voltage of 1–20 kV, is scanned on the specimen surface. Scanning electron microscopy (SEM) is giving morphological examination with direct visualization. The techniques based on electron microscopy offer several advantages in morphological and sizing analysis; however, they provide limited information about the size distribution and true population average. For SEM characterization, nanoparticles solution should be first converted into a dry powder, which is then mounted on a sample holder followed by coating with a conductive metal, such as gold, using a sputter coater. The sample is then scanned with a focused fine beam of electrons (Jores et al. 2004). The surface characteristics of the sample are obtained from the secondary electrons emitted from the sample surface. The nanoparticles must be able to withstand vacuum, and the electron beam can damage the polymer. As the electron beam strikes the surface, a large number of
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signals are generated from (or through) the surface in the form of electrons or photons. These signals emitted from the specimen are collected by detectors to form images and the images are displayed on a cathode ray tube screen. The mean size obtained by SEM is comparable with results obtained by dynamic light scattering. Moreover, these techniques are time consuming, costly and frequently need complementary information about sizing distribution (Molpeceres et al. 2000).
1.6.5 TEM TEM operates on different principle than SEM, yet it often brings same type of data. The sample preparation for TEM is complex and time consuming because of its requirement to be ultra-thin for the electron transmittance. The nanoparticles dispersion is deposited onto support grids or films. To make nanoparticles withstand the instrument vacuum and facilitate handling, they are fixed using either a negative staining material, such as phosphotungstic acid or derivatives, uranyl acetate, etc., or by plastic embedding. Alternate method is to expose the sample to liquid nitrogen temperatures after embedding in vitreous ice. The surface characteristics of the sample are obtained when a beam of electrons is transmitted through an ultra-thin sample, interacting with the sample as it passes through (Molpeceres et al. 2000). 1.6.5.1 Basic Principle of TEM The contrast in a TEM image is not like the contrast in a light microscope image. In the crystalline sample interacts with the electron beam mostly by diffraction rather than by absorption. The intensity of the diffraction depends on the orientation of the planes of atoms in a crystal relative to the electron beam; at certain angles the electron beam is diffracted strongly from the axis of the incoming beam, while at other angles the beam is largely transmitted. Modern TEMs are equipped with specimen holders that allow to tilt the specimen to a range of angles in order to obtain specific diffraction conditions. Therefore, a high contrast image can be formed by blocking electrons deflected away from the optical axis of the microscope by placing the aperture to allow only unscattered electron through. This produces a variation in the electron intensively that reveals information on the crystal structure. This technique, particularly sensitive to extended crystal lattice defects, is known as “bright field or light field.” It is also possible to produce an image from electron deflected by a particularly crystal plane which is known as a dark field image. The specimens must be prepared as a thin foil so that the electron beam can be penetrated. Materials that have dimensions small enough to be electron transparent, such as powders or nanotubes, can be quickly produces by the deposition of a diluted sample containing the specimen onto support grids. As polymeric nanocomposites or textiles samples are not as hard as metals, they are cut into thin films
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