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Biotechnology Fundamentals, 3rd Third Edition Firdos Alam


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Biotechnological Applications in Human Health Provash


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Nanomaterials in energy and environmental applications 1st


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applications in cardiovascular health First Edition
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nanomaterials 1st Edition Chaudhery Mustansar Hussain

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nanomaterials 1st Edition Chaudhery Mustansar Hussain
Applications of
Nanomaterials in
Human Health

Firdos Alam Khan


Editor

123
Applications of Nanomaterials in Human
Health
Firdos Alam Khan
Editor

Applications
of Nanomaterials
in Human Health
Editor
Firdos Alam Khan
Department of Stem Cell Biology
Imam Abdulrahman Bin Faisal University
Dammam, Saudi Arabia

ISBN 978-981-15-4801-7    ISBN 978-981-15-4802-4 (eBook)


https://doi.org/10.1007/978-981-15-4802-4

© Springer Nature Singapore Pte Ltd. 2020


This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
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Singapore
Preface

Over the past few years, there has been tremendous interest in the nanomaterials
field because of their nanosize, better biocompatibility, better targeting of the dis-
ease and most important is the effective treatments of many diseases. The nanoma-
terials have revolutionized almost all the fields, especially their applications in the
biomedical sciences are the most promising ones. The nanomaterials are synthe-
sized by using different methods and they can be obtained from both natural and
synthetic sources. One of the remarkable characteristics of these nanomaterials is
that they can be conjugated, linked, and encapsulated with other materials, chemi-
cals, drugs, and molecules, which make them most attractive for various biological
applications. Over the past few years, several nano-based products have been cre-
ated for many clinical conditions. There are many more under different phases of
the trials (preclinical or clinical) for a variety of biological applications such as drug
delivery, diagnosis, and treatment. As the field of nanotechnology is expanding, we
thought it is time to overview the impact of the nanomaterials on human health and
to write an exclusive book dedicated towards the application of nanomaterials in
human health. This book provides comprehensive and updated information on all
aspects of the nanomaterials related to human health. There are many books written
on the application of nanomaterials on different topics, but there is no single book
available that discusses all topics of nanomaterials related to human health.
In this book, we have tried to include all the topics which are directly or indi-
rectly related to fields of nanomaterials. The primary objective of this book is to
provide the students, researchers, and professionals a single source of information
about different nanomaterials and their biological and medical applications. There
are 15 chapters in this book and each chapter contains the updated information with
beautiful illustrations. We have discussed the various topics like nanomaterials and
their types and classifications, synthesis of nanomaterials, and characterization of
nanomaterials. The topics such as application of nanomaterials in stem cells, tissue
engineering and regenerative medicine, neuronal differentiation, neuronal protec-
tion, neurotoxicity, neurological diseases, diagnosis and treatment of genetic disor-
ders, cancer diagnosis, drug delivery, treatment of microbial and viral infections,
treatment of endocrine diseases have also been discussed. We have also discussed

v
vi Preface

major nano-based products related to nanomedicine, nanosensors, nanorobots,


nanodiagnostics, commercialization of nanomaterials, IPR, and marketing of nano-
products. In addition, we have also explained the negative effects of nanomaterials
on human health along with ethical issues. The last chapter deals with the next-­
generation nanomaterials—smart nanomaterials.

Dammam, Saudi Arabia Firdos Alam Khan


Acknowledgments

No one walks alone in the journey of life, but when one is walking, it is where you
start to thank those that joined you, walked beside you, and helped you along the
way. First, I am grateful to the Almighty Allah who gave me the strength to com-
plete this edition of the book in the stipulated time. I am thankful to many people,
especially to Dr. Bhavik Sawhney, Editor-Biomedicine, Springer Nature who sup-
ported me to complete the task and to all the production team members of Springer
Nature especially to Mr. Salmanul Faris Nedum Palli for the support and cooperation.
I am grateful to all the authors and especially to all the corresponding authors,
namely Prof. Ebtesam Al-Suhaimi, Prof. Shahid Siddiqui, Prof. Peter Hollands,
Prof. Samuel Sam, Dr. Sultan Akhtar, Dr. Alaa A A Aljabali, Dr. Adeeb Shehzad, Dr.
Amani Alhibshi, Dr. Ayman Vakil, Dr. Santhini Elango, Dr. Vijaya Ravi Nayagim,
and Dr. Suresh Thangudu for their immense contributions and timely completion of
the work.
I would like to thank the entire management team of Institute for Research and
Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University,
Dammam, Saudi Arabia for their support, especially to Professor Ebtesam
Al-Suhaimi, Dean, IRMC, Imam Abdulrahman Bin Faisal University, Dammam,
Saudi Arabia for her constant encouragement.
I am thankful to all my teachers and mentors especially to Professor Nishikant
Subhedar and Late Professor Obaid Siddiqi FRS for their immense contributions in
shaping my research career. I am also thankful to all my friends, well-wishers, and
colleagues for their support and cooperation.
I am grateful to my entire family members, especially to my father (late)
Nayeemuddin Khan and mother Sarwari Begum, my brothers (Aftab Alam Khan,
Javed Alam Khan, Intekhab Alam Khan, and Sarfaraz Alam Khan), my sisters
(Syeeda Khanum, Faheemida Khanum, Kahkashan Khanum, and Aysha Khanum),
my wife Samina Khan, my sons (Zuhayr Ahmad Khan, Zaid Ahmad Khan, and
Zahid Ahmad Khan) and daughter (Azraa Khan), and my father-in-law (Abdul
Qayyum Siddiqi) and mother-in-law (Uzma Siddiqi). All of them, in their own
ways, supported me.
Enjoy reading!

vii
Contents

1 Nanomaterials: Types, Classifications, and Sources����������������������������    1


Firdos Alam Khan
2 Synthesis of Nanomaterials: Methods & Technology ��������������������������   15
Firdos Alam Khan
3 Characterization of Nanomaterials: Techniques and Tools ����������������   23
Sultan Akhtar and Sadaqat Ali
4 Application of Nanomaterials: Overview and Historical
Perspectives����������������������������������������������������������������������������������������������   45
Samuel Sami-Howard
5 Application of Nanomaterials in Stem Cells, Tissue Engineering
and Regenerative Medicine ��������������������������������������������������������������������   65
Peter Hollands
6 Applications of Nanomaterials in Neurological Diseases, Neuronal
Differentiation, Neuronal Protection, and Neurotoxicity ��������������������   83
Amani H. Alhibshi, Widyan A. Alamoudi, and Rai K. Farooq
7 Application of Nanomaterials in the Diagnosis and Treatment of
Genetic Disorders������������������������������������������������������������������������������������ 125
Alaa A. Aljabali, Mohammad A. Obeid, Haneen A. Amawi,
Meriem M. Rezigue, Yassmen Hamzat, Saurabh Satija,
and Murtaza M. Tambwala
8 Application of Nanomaterials in Cancer Diagnosis, Drug Delivery,
and Therapy���������������������������������������������������������������������������������������������� 147
Shahid S. Siddiqui, Mashael Saeed Al-Qahtani, Faisal Ahmed Khalil
Al Allaf, Loganathan Sivakumar, and Zeba Kidwai Siddiqui
9 Application of Nanomaterials in Treatment of Microbial and Viral
Infections�������������������������������������������������������������������������������������������������� 173
Adeeb Shehzad, Raheem Shahzad, Hanan Aldossary,
and Ebtesam A. Al-Suhaimi

ix
x Contents

10 Application of Nanomaterials in Treatment of Endocrine Diseases������ 191


Khulood M. Al-Khater and Ebtesam A. Al-Suhaimi
11 Major Nano-based Products: Nanomedicine, Nanosensors,
and Nanodiagnostics�������������������������������������������������������������������������������� 211
Firdos Alam Khan
12 NANOMATERIALS: Global Research Publication,
Research Quality, and Patent Trends���������������������������������������������������� 229
Ayman Akil and Walid Hassan
13 Nanomaterials and Their Negative Effects on Human Health������������ 249
Vijaya Ravinayagam and B. Rabindran Jermy
14 Nanomaterials and Ethical Issues���������������������������������������������������������� 275
Oodhimalai Elango Santhini and Selvaraj Dinesh Kirupha
15 Next Generation Nanomaterials: Smart Nanomaterials,
Significance, and Biomedical Applications�������������������������������������������� 287
Suresh Thangudu
About the Editor

Firdos Alam Khan is a Professor and Chairman of the Department of Stem Cell
Biology, Institute for Research and Medical Consultations (IRMC), Imam
Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. He completed his
Ph.D. in Zoology with a specialization in Neuroscience at Nagpur University, India,
and has been involved in teaching various courses including Cell Biology,
Pharmacology, Business of Biotechnology, Biomedicine, Cell and Tissue
Engineering, and Bioethics and IPR to undergraduate and postgraduate students. He
was a Professor and Chairman of the School of Life Sciences and served as Chairman
of the Research and Development program at Manipal University (now Manipal
Academy of Higher Education), Dubai Campus, United Arab Emirates. He holds
three US patents in the field of stem cell biology, has authored two books:
Biotechnology Fundamentals (textbook) and Biotechnology in Medical Science,
and has published numerous research articles on stem cell biology, neuroscience,
and nanomedicine. He is an editor and reviewer for various high-impact journals,
including Scientific Reports, Nanomedicine, IET Nanobiotechnology, Drug Design,
Development and Therapy, 3 Biotech, Journal of Biomolecular Structure and
Dynamics, and the International Journal of Nanomedicine.

xi
Nanomaterials: Types, Classifications,
and Sources 1
Firdos Alam Khan

Abstract

Over the past few years, nanomaterials (NMs) have attracted the research-
ers because of their nanosize, physical, biological, and chemical properties com-
pared to their bulk materials. These NMs are classified based on their size,
chemical composition, shape, and sources. Different types of NMs have been
synthetized from different sources and they are being classified accordingly.
Many NMs have been produced in large quantities based on the requirements for
many industrial applications. The two main sources through which NMs are
being produced are synthetic source and naturally occurring nanoparticles (NPs).
In this chapter, we discuss the types and classifications of NMs and broadly dis-
cuss the different types of nanomaterials isolated from natural and synthetic
sources.

Keywords

Nanomaterials · Types · Classifications · Sources

1.1 Introduction

Nanoparticles (NPs) and nanomaterials (NMs) have attracted many researchers due
to their unique properties such as nanosize, better biocompatibility and bioavail-
ability, and most importantly their effective drug delivery capabilities. There are
many factors which are responsible to make these NPs and NMs the most desirable

F. A. Khan (*)
Department of Stem Cell Biology, Institute for Research & Medical Consultations, Imam
Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
e-mail: [email protected]

© Springer Nature Singapore Pte Ltd. 2020 1


F. A. Khan (ed.), Applications of Nanomaterials in Human Health,
https://doi.org/10.1007/978-981-15-4802-4_1
2 F. A. Khan

candidates for many biological and medical applications. Some of them are better
thermal and electrical conductivity, better catalytic activity, and better light absorp-
tion capabilities. The definition of nanomaterials is basically related to their sizes
and the materials which have diameter from 1 to 100 nm are normally known as the
nanomaterials and nanoparticles. There are several rules and regulation to measure
the diameter of NPs and NMs are being used by the researchers in European Union
(EU) and the USA, however, there is no specific accepted definition for nanomateri-
als does not exist. In addition, different establishments have different definitions of
nanomaterials (Boverhof et al. 2015).
As per Environmental Protection Agency (EPA) nanomaterials display excep-
tional properties different than the equivalent chemical compounds (United Nations
2014). In addition, the US FDA also denotes to nanomaterials as materials that have
at least one dimension from 1 to 100 nm and exhibit dimension dependent phenom-
ena (US-FDA 2016). Correspondingly, International Organization for
Standardization (ISO) has named nanomaterials as a material having internal
nanoscale surface structure (ISO/TS 2010). The nanomaterials such as nanospheres,
nanoplates, quantum dots, nanowires, nanofibers, and other NMs have been defined
based on this ISO definition (Bleeker et al. 2012). Likewise, the word “nanomate-
rial” is called as a produced or natural material that gets unbound, agglomerated
materials where external dimensions are between 1 and 100 nm ranges according to
the EU Commission (Potocnik and Off 2011). The British Standards Institution has
suggested the definitions (Table 1.1) for the nanomaterials:
The field of nanotechnology is growing rapidly, and tremendous amount of NMs
have been produced over the past few years, and it caused many challenges in many
countries’ as the laws for the NMs are not well established and accepted materials
for the biological applications. This is the major hurdle for many nanomaterial pro-
ducing companies which produce materials for biological and biomedical

Table 1.1 Definitions as per the British Standards Institution


Nomenclature Definition
Nanoscale 1–1000 nm range
Nanoscience The study of matter that deals with size and structure-dependent
properties
Nanotechnology Modification of materials on the nanoscale dimension for the industrial
and biomedical applications
Nanomaterials Materials with internal or external structures on the nanoscale dimension
Nanoparticles Materials with three external nanoscale dimensions

Nanofibers Two similar exterior nanoscale dimensions and a third larger dimension
are present in a nanomaterial, it is referred to as nanofiber
Nanocomposites The combination of two or more nanomaterials is called as
nanocomposites
Nanostructured Materials containing internal or surface nanostructure
materials
1 Nanomaterials: Types, Classifications, and Sources 3

applications. It is a big challenge to nanomaterials producing companies to get easy


approval for the biological applications.

1.2 Types and Classifications

As the field of nanotechnology is growing rapidly, tremendous amount of NMs have


been produced and all these NMs must be identified based on the structure, shapes,
size, and chemical synthesis in order to differentiate from each other. Interestingly,
NMs can be broadly classified into four categories which are described below.

1.2.1 Carbon Nanomaterials

The NMs which contain carbon are called carbon nanomaterials, and these carbon
nanomaterials can be synthetized in different shapes such as (1) hollow tubes or (2)
spheres (Kumar and Kumbhat 2016). In addition, carbon nanofibers, graphene,
fullerenes, carbon black, carbon nanotubes, and carbon onions are also classified as
carbon nanomaterials (Fig. 1.1).

1.2.2 Metal and Metal Oxide Nanomaterials

The metal and metal oxide can also be used to produce NMs which are called as
metal and metal oxide nanomaterials or inorganic nanomaterials. Some of these
NMs are gold (Au), silver (Ag) nanomaterials and metal oxides-based nanomateri-
als are titanium dioxide (TiO2) and zinc oxide (ZnO) nanomaterials.

Fig. 1.1 Different carbon-based nanomaterials


4 F. A. Khan

1.2.3 Organic Nanomaterials

This type of NMs mostly contains organic matter, without carbon or inorganic based
nanomaterials. One of the characteristics of these organic nanomaterials is that they
possess noncovalent bonds (weak in nature, which can be easily broken). These
organic materials can be easily modified to produce different shapes of nanomateri-
als like liposomes, dendrimers, micelles, and polymers (Fig. 1.2).

1.2.4 Nanocomposites

The combination of one type of nanomaterials with another type of nanomaterials is


called as nanocomposites. The nanomaterials either combine with other types of
nanowires, nanofibers, or can be combined with larger size materials. These nano-
composites may be any combinations of metal-based, carbon-based, or organic-­
based nanowires, nanofibers, with any form of ceramic, metal, polymer bulk
materials (Fig. 1.3).

Fig. 1.2 Different types of organic nanomaterials

Fig. 1.3 Structure of nanocomposites


1 Nanomaterials: Types, Classifications, and Sources 5

1.3 Classification of Nanomaterials

1.3.1 Dimensions and Sizes

As different types of nanomaterials are produced for a variety of applications, it


becomes necessary to categorize these nanomaterials for proper applications. The
nanomaterials are mostly solid particles, and their size and dimensions can be easily
measured by using different methods. The idea for classification of nanomaterials
was proposed by a scientist in the year 2000 (Gleiter 2000), he classified the nano-
materials based on their crystalline forms and chemical compositions. Still, this
method of measuring was not fully complete as it did not measure dimensions of the
nanomaterials (Tiwari et al. 2012). In another study, different groups of researchers
have made a new classification which was primarily based on 0 Dimension, 1
Dimension, 2 Dimension, and 3 Dimension nanomaterial (Pokropivny and
Skorokhod 2007).
The classification of nanomaterial is basically dependent on the movement of
electrons in the nanomaterial. The presence of electrons is generally fixed in “0”
dimension nanomaterials, whereas for “1” dimension nanomaterials, electrons can
move freely along the x-axis, which is commonly less than 100 nm. Similarly, “2”
dimension and “3” dimension nanomaterials have better electron movements along
the x- to y-axis or x-, y-, z-axis, respectively. It has been found that the ability to
predict the properties of nanomaterials determines the classification of the nanoma-
terials. Moreover, the characteristics of nanomaterials are basically dependent on
the grain boundaries as per the Gleiter’s classification, whereas the classification by
Pokropivny and Skorokhod suggested that the characteristics of nanomaterials are
ascribed to the nanoparticle shapes and dimensionalities (Pokropivny and
Skorokhod 2007).

1.3.2 Origin of Nanomaterials

The nanomaterials can be classified based on their source of origin, which means,
the source materials to produce nanomaterials. They can be classified as naturally
origin nanomaterials or synthetically produced nanomaterials.

1.3.2.1 Natural Nanomaterials


Natural nanomaterials can be formed in biological species such as microbes, or
plants and also through anthropogenic actions. The creation of natural nanomateri-
als is an accessible process as they are present in the hydrosphere, atmosphere,
lithosphere, and biosphere. Interestingly, our planet is comprised of nanomaterials
that are naturally formed and are present in the rivers, groundwater oceans, lakes,
rocks, soils, magma, or lava as well as in the microbial organisms and also in
humans (Hochella Jr et al. 2015; Sharma et al. 2015).
6 F. A. Khan

1.3.2.2 Synthetic Nanomaterials


The most widely used method to make nanomaterials is the synthetic method, which
allows the production of nanomaterials by biological, physical, chemical, or hybrid
methods. One of the advantages of the synthetically produced nanomaterials is that
it is possible to produce large quantity of nanomaterials with different shapes and
sizes. Another important aspect of the synthetic method is that different chemicals
or reagents can be linked or conjugated with nanomaterials accurately and precisely.
The major concern among synthetically designed nanomaterials is whether present
knowledge is sufficient to envisage their performance. In addition, they display a
different environment behavior, which is different from natural nanomaterials.
Presently, diverse sources of nanomaterials are produced for various biological
applications (Wagner et al. 2014).

Byproduct Nanomaterials
The nanomaterials produced incidentally as a byproduct of industrial processes
(motor vehicle engine and combustion processes) are called as subsidiary nanoma-
terials. These nanomaterials can also be produced by forest fires and trees burning.
However, naturally produced nanomaterials can be found in the bodies of animals,
insects, plants, and humans. Nonetheless there is a difference between naturally
occurring or incidental and synthetically designed nanomaterials. In a few cases,
incidental nanomaterials can be considered as a subcategory of natural
nanomaterials.
The molecules are made up of atoms and these molecules and atoms are the basic
components of all living and non-living organisms. The atoms and molecules are
naturally manipulated several times to be able to make nanomaterials. The inciden-
tal and naturally occurring nanomaterials are constantly being made and dispersed
in underground, water, and atmosphere. One of the main differences between inci-
dental and synthetic nanomaterials is that the structure and morphology of syntheti-
cally produced nanomaterials can be better controlled as compared to incidental
nanomaterials. Additionally, it is also possible to modify the shape and size of the
synthetic nanomaterials which is however not possible in the case incidental nano-
materials. The metallic-based nanomaterials can also be produced from synthetic
methods.

Natural Nanomaterials
There are many ways to produce nanomaterials like eruption of volcanos, forest
fires, and tree burning. In addition, some of the natural nanomaterials can be
obtained from skin and hair shedding of plants and animals. In addition, volcanic
eruptions, dust storms, and forest fires are the main sources from where high quanti-
ties of nanomaterials are produced that drastically affect the air quality of the planet.
Likewise, industrial operations, and transportation are some of the human activities
that also caused the production of nanomaterials. It has been reported that 10% of
overall aerosols in the environment are produced by humans, while the remaining
90% of atmospheric aerosols were produced by natural method (Taylor 2002).
1 Nanomaterials: Types, Classifications, and Sources 7

Dusts and cosmic dusts for (Eagle Nebula stars which are 6500 light years away
from the earth) are also good sources of nanomaterials (Barnard and Guo 2012).
The analysis by “astronomical infrared spectroscopy” has revealed that dost of
clouds contained nitride, silicate, carbide, oxide, carbon, and organic-based nano-
materials (Barnard and Guo 2012). Interestingly, the diamond with nanometers size
was discovered in the Murchison meteorite (Dai et al. 2002). Different types of
nanomaterials are present throughout the world which are present in either mixed
form or sorted forms. The impact of spectacular temperature variations, electromag-
netic radiation, pressure gradients, physical collisions, and shock waves is generally
responsible for formation of nanomaterials in the space (Barnard and Guo 2012).
This precedes to the largest range of nanoscale materials with distinct isomerization
and chemical spectrum (Hochella Jr et al. 2015). The satellite images showed that
dust storms can move from one region to another region which can also be respon-
sible for migration of nanominerals. It has been found that about more than fifty
percentage of the atmospheric aerosol particles are in the size between 100 and
200 nm (d’Almeida and Schütz 1983; Shi et al. 2005).

1.3.2.3 Engineered Nanomaterials


The engineered nanoparticles are those which are being produced due to combus-
tion from cooking, petrol, and diesel transportation and coal for power generation
(Linak et al. 2000), chemical and industrial manufacturing, oil or re-refining (Rogers
et al. 2005). These nanomaterials mostly contain carbon (De Volder et al. 2013),
TiO2 (Weir et al. 2012), and hydroxyapatites (Sadat-Shojai et al. 2010) which are
used in the sports, cosmetics, and toothpaste production. Consequently, these syn-
thetic nanomaterials are a new category of nanomaterials that may cause adverse
environmental and human health effects (Kagawa 2002). The automobile transpor-
tation, diesel engines release 20–130 nm sized nanoparticles, whereas gasoline
engines release 20–60 nm sized nanoparticles (Westerdahl et al. 2005; Sioutas et al.
2005). More than 90% of carbon nanomaterials present in the atmosphere are die-
sel-based nanoparticles (Kittelson 2001).
There are many applications of nanomaterials in the healthcare sectors, and they
are being used in the production of cosmetics, personal, and healthcare applications.
Generally, nanomaterials used in commercial applications are basically engineered
nanomaterials and they are produced by using chemical, biological, and physical
methods. Besides cosmetics, nanomaterials have been widely used in commercial
product development ranging from personal care products to industrial products.
For example, titanium oxide nanomaterials with100 nm and above sizes are gener-
ally used in cosmetics and sunscreen production. Likewise, silver nanomaterials are
used in different applications including food storage containers, shampoos, air sani-
tizer sprays, wet wipes, and toothpastes.

1.3.2.4 Naturally Produced Nanomaterials


There are different types of nanomaterials which are present in living creatures such
as plants, insects, birds, bacteria, algae, viruses, animals, and humans. Latest
advancement in the field of anatomical and analytical techniques helps the
8 F. A. Khan

researchers to visualize nanomaterial’s morphology with minute details, which in


fact will eventually lead to a better understanding of these creatures. The knowledge
about the presence of nanomaterials in these creatures helps the researchers to use
them for the derivation and isolation of nanomaterials for various biomedical appli-
cations. For example, insects have nanomaterials which help them to stay alive in
severe living or environmental conditions. In addition, plants use the nutrients avail-
able in the soil and water for their growth, which leads to the accumulation of these
minerals in nanoform in their bodies. Moreover, animals and small insects utilize
nanomaterials for their protection from predatory animals. Likewise, humans also
have body organs that are primarily made up of nanomaterials such as bones, anti-
bodies, and enzymes. The nanomaterials help the body to perform normal physio-
logical functions. Moreover, DNA or RNA which are genetic materials in the
animal/human cell are also made up of nanosize materials. This obviously shows
that nanomaterials are the basis for life forms on earth. These nanoscale organisms
are found in nanobacteria, viruses, fungi, algae, and yeast.
Among different species, viruses are the largest communities which can be a
non-living catalyst and can also be a living organism inside host cells. Generally, the
viruses cause diseases in plants, animals, and humans (Duckworth and Gulig 2002;
Picó et al. 1996; Berg 2000; Uchiyama 1997). With the help of molecular biology
tools and techniques it is now possible to genetically alter or tailor viruses for vari-
ous applications. These viruses can selectively enter into smaller molecules and
cause diseases and other problems (Flenniken et al. 2003; Flenniken et al. 2006).
These viruses can be used in the synthesis of specialized nanomaterials (Strable and
Finn 2009). There are few studies which showed that viruses can be used to produce
novel nanomaterials (Langeveld et al. 2001; Wang et al. 2002).
Bacteria can bind to toxic surface of the heavy metals which can be precipitated
to produce metal nanomaterials. They are called as nanobacteria. These nanobacte-
ria are useful in the biosynthesis of low toxicity nanomaterials (Southam and Donald
1999). One of such nanobacteria Pseudomonas stutzeri A259 was first used bacteria
in the production of silver nanomaterials (Haefeli et al. 1984). There are many
metallic nanomaterials like gold nanomaterials, alloy nanomaterials, nonmagnetic
nanomaterials, and metal sulfide quantum dots and ZnS (Slocik et al. 2004; Nair and
Pradeep 2002; Senapati et al. 2005 Zheng et al. 2010; Jha et al. 2009a, b; Bansal et al.
2006; Narayanan and Sakthivel 2010; Sweeney et al. 2004; Mandal et al. 2006)
can be synthesized by using different strains of bacteria. Moreover actinomycetes
were also used to produce nanomaterials. The bacteria-­based nanomaterial forma-
tion method is highly useful in a nanomedicine as they cause less cellular toxicity
(Li et al. 2011). Nevertheless, the major disadvantages of these bacterial-based
nanomaterials are that process is time-consuming and they are difficult to filter and
produce a low yield as compared to chemically synthesized method (Jeevanandam
et al. 2016).
In addition, nano-organisms are also called as nanobes and they are gaining
interest as they were discovered during off-shore petroleum exploration in Australia
(Uwins et al. 1998). These nanobes encompasses carbon, nitrogen, oxygen,
1 Nanomaterials: Types, Classifications, and Sources 9

membrane-­bound structure with dense cytoplasm. The uniqueness of these nanobes


is their size and that they were found in Martian meteorite ALH84001 (Urwins 2000).
The nanomaterials can also be created by magnetotactic bacteria and they are
highly effective to produce magnetic oxide nanomaterials that possess unique prop-
erties such as super-paramagnetism, high coercive force, and micro-configuration.
These magnetic oxide nanomaterials can be used in various biological and biomedi-
cal applications (Li et al. 2012). Normally, biocompatible magnetite iron oxide, iron
sulfides, and maghemite can be synthesized by using magnetotactic bacteria
(Bazylinski et al. 1994; Bazylinski et al. 1995). They can be used in the cancer treat-
ment through magnetic hyperthermia and magnetic resonance imaging (MRI) (Fan
et al. 2009). Additionally, surface distributed magnetic iron-sulfide particles, modi-
fied iron nanomaterials, magnetic octahedral nanomaterials, and superparamagnetic
nanomaterials can be produced by using magnetotactic bacteria (Watson et al. 1999;
Zhang et al. 1998; Roh et al. 2001; Philipse and Maas 2002; Lee et al. 2004; Arakaki
et al. 2008).
The shapes of different bacteria also play a critical role in the nanomaterial’s
formation, for example, ovoid, vibrio, cocci, spirilla, rod-shape, and multicellular
bacteria possess unique characteristics in producing nanomaterials (Arakaki et al.
2008; Blakemore 1982; Thornhill et al. 1995; Spring and Schleifer 1995).
Nanomaterials can also be produced from algae, fungi, yeast, and bacterial
spores. It has been reported that algae like Chlorella vulgaris supports the formation
of silver nanomaterials (Hosea et al. 1986). Similarly, phytochelatin-coated CdS
and nanocomposite and nanoporous structures can be produced by Phaeodactylum
tricornutum and by coccoliths and diatoms (Scarano and Morelli 2003). It has been
reported that fungi are excellent candidates for the synthesis of metal and metal
sulfide nanoparticle. The molecular mechanism through which they help to produce
nanomaterials is not well understood (Krumov et al. 2009).
It has been found that fungi which comprise a range of enzymes are responsible
for providing the shapes of the nanomaterials. Furthermore, another fungus,
Fusarium oxysporum and Verticillium species were used for the synthesis of gold,
silver, and gold–silver alloy nanomaterials (Mukherjee et al. 2002; Bansal et al.
2004). Furthermore, enzymes present in the Fusarium oxysporum also helped the
synthesis of Cadmium quantum dots (Ahmad et al. 2002; Dameron et al. 1989).
Additionally, Candida glabrata, Torulopsis species, and Schizosaccharomyces
pombe were used in the synthesis of Cadmium sulfur quantum dots (Reese and
Winge 1988), lead sulfur nanocrystals, and silver nanomaterials, respectively.

1.3.2.5 Plant Based Nanomaterials


Nanomaterials can be derived from the plants as they are considered as excellent
source of cellular bio-composites. It has been found that natural fibers are compos-
ites of cellulosic fibrils with 100–1000 nm long containing both crystalline and
amorphous segments. The excellent strength and performance properties of natural
fibers are due to their elementary structure with nano-fibrillar components (Lucia
and Rojas 2009). The isolation of nanocellulose can be done by mechanical,
10 F. A. Khan

chemical methods (Mohammadinejad et al. 2016). The plant has many structural
features such as plant leaves contain nanostructures that are used for several pur-
poses such as insects sliding, mechanical stability, increased visible light, and harm-
ful UV reflection and radiation absorption (Gorb et al. 2005; Bargel et al. 2006;
Barnes and Cardoso Velhena 1996; Pfündel et al. 2008). The most famous nanoma-
terial property in plants is the super-hydrophobicity in lotus leaves that helps in
self-cleaning and super-­wettability of the leaves (Barthlott and Neinhuis 1997).
Several studies have suggested that piles of nanomaterials are responsible for the
circular layer in plants and insects which allows them to float on water without sink-
ing (Nguyen et al. 2014; Xu et al. 2014). Taking this information, many artificial
super-hydrophobic materials with self-cleaning ability have been produced [196]
using electrodeposition, photolithography, and colloidal methods (Madou 2002;
Ming et al. 2005; Chow 2007).

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Synthesis of Nanomaterials: Methods &
Technology 2
Firdos Alam Khan

Abstract

Nanomaterials are synthetized by different methods based on the types and


nature of the nanomaterials. In a broad sense “top-down” and “bottom-up” are
the two foremost methods to synthesize nanomaterials. In top-down method bulk
materials have been reduced to nanomaterials, and in case of bottom-up method,
the nanomaterials are synthesized from elementary level. The different methods
which are being used to synthesize nanomaterials are chemical vapor deposition
method, thermal decomposition, hydrothermal synthesis, solvothermal method,
pulsed laser ablation, templating method, combustion method, microwave syn-
thesis, gas phase method, and conventional Sol-Gel method.

Keywords

Nanomaterial synthesis · Methods · Techniques

2.1 Introduction

Over the past couple of decades, various methods of preparation and synthesis of
nanomaterials have been developed. The main objectives of the synthesis of nano-
materials is to ensure that for what purpose these nanomaterials are being synthe-
sized. The researchers should know the applications of the nanomaterials so that
they can synthesize them accordingly. The method of production of nanomaterials
to be used in the industrial application for the development of various products will

F. A. Khan (*)
Department of Stem Cell Biology, Institute for Research & Medical Consultations, Imam
Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
e-mail: [email protected]

© Springer Nature Singapore Pte Ltd. 2020 15


F. A. Khan (ed.), Applications of Nanomaterials in Human Health,
https://doi.org/10.1007/978-981-15-4802-4_2
16 F. A. Khan

be different than the method of production to be used in biological or medical appli-


cations. Other objectives of the researchers to synthetize nanomaterials are better
functionality and lower cost. Over the past few years, several physical and chemical
methods have been used to improve the performance of nanomaterials demonstrat-
ing enhanced properties (Shibata et al. 1998).

2.2 Methods to Synthesize Nanomaterials

The “top-down” and “bottom-up” are the two major methods which have been used
to successfully synthesize nanomaterials. We have described these methods in fur-
ther detail (Fig. 2.1).

2.2.1 Production of Nanomaterials by Top-Down Method

In this method, solid and state processing of the materials are mostly used and this
method involves breaking of the bulk material into smaller particles using physical
processes such as crushing, milling, and grinding methods. Generally, this method
is not appropriate for formulating evenly shaped nanomaterials, and it is very diffi-
cult to get very small size nanoparticles even with high energy usages. The major
difficulty of this method is the shortage of the surface structure as it has significant

Fig. 2.1 Diagrammatic representation of top-down approach and bottom-down approach of mak-
ing of nanomaterials
2 Synthesis of Nanomaterials: Methods & Technology 17

Fig. 2.2 Diagrammatic representation of hydrothermal process of nanoparticle production

impact on physical properties and surface chemistry of nanomaterials. In addition,


this method also causes substantial crystallographic loss to the processed shapes.

2.2.2 Production of Nanomaterials by Bottom-Up Method

In this method, materials are prepared by atom-by-atom or molecule-by-molecule


to make large amount of materials. This method is more frequently used for produc-
ing most of the nanomaterials. This method has an ability to produce a uniform size,
shape, and well- distributed nanomaterials. It basically control the chemical synthe-
sis process in a precisely manner to prevent undesirable particle growth. This
method plays an important role in the production and processing of nanomaterials
with better particle size distribution and better morphology. Another important fea-
ture is that its an environment friendly and economical processes for the nanoparticle
production (Hahn 1997). There are many approaches for synthesizing nanomateri-
als like hydrothermal (Cheng et al. 1995; Yin et al. 2001), combustion synthesis
(Nagaveni et al. 2004a), gas-phase methods (Jones et al. 2003; Wang et al. 2005),
microwave synthesis, and sol-gel processing (Watson et al. 2004), which we have
described below.

2.2.2.1 Hydrothermal Method


The hydrothermal method is normally done in a pressurized container which is
called as an “Autoclave” where temperature and pressure can be controlled and
regulated. During nanomaterial synthesis, the temperature can be increased at the
boiling point of water, which allows the vapor to get saturated. This method
(Fig. 2.2) has been extensively used in the production of different nanoparticles
(Yang et al. 2001). The advantage of this method is that this can be useful to control
material size, particle morphology, crystalline phase, and surface chemistry through
regulation of the reaction temperature, pressure, solvent properties, solution compo-
sition, and additives (Carp et al. 2004).
18 F. A. Khan

Fig. 2.3 Diagrammatic


representation of
solvothermal process of
nanoparticle production

2.2.2.2 Solvothermal Method


The solvothermal method (Fig. 2.3) is like hydrothermal method, the only differ-
ence is that it uses different solvents other than water. Interestingly, this method is
more effective in synthesis of nanomaterials with good distribution, especially when
organic solvents or chemicals with high boiling points are selected. Moreover, this
method provides better controlling method to produce better size and shapes of the
materials than the hydrothermal method. This method synthetizes nanomaterials or
nanorods with or without the addition of surfactants.

2.2.2.3 Chemical Vapor Deposition Method


The chemical vapor deposition (CVD) method is used to manufacture high perfor-
mance thin nano-films. In this method, substrate is basically treated with volatile
precursors which act on the substrate surface to produce the desirable films. Usually,
volatile by-products are eliminated by gas flow through the reaction chamber. The
quality of the deposited materials on the surface is greatly dependent on several fac-
tors like temperature, rate of reaction, and the amount of the precursors (Kim et al.
2004). It has been reported that Sn4+doped TiO2 nanoparticle films were produced
by CVD method (Cao et al. 2004). Another doped TiO2 nanoparticle was synthe-
sized by CVD method where TiO2 is crystallized into the rutile structures depending
on the type and number of cations present in the chemical reactions (Gracia et al.
2004). The advantage of this method is getting consistent glaze of the nano film, but
this method has many limitations including higher temperatures required for chemi-
cal reactions, and secondly it is difficult to scale up (Sudarshan 2003).

2.2.2.4 M  ethod of Thermal Decomposition and Pulsed


Laser Ablation
The doped metals can be produced by using decomposing metal alkoxides, salts,
heat or electricity. Moreover, the properties of nanomaterials strongly depend on the
2 Synthesis of Nanomaterials: Methods & Technology 19

flow rate of the precursor’s concentrations in the reactions and its environment. It
has been reported that TiO2 nanoparticles with a diameter < 30 nm can be synthe-
tized by using the thermal decomposition of titanium alkoxide at 1200°Celsius tem-
perature (Kim et al. 2005). In another study, TiO2 nanoparticles with a diameter
(3–8 nm) were produced by pulsed laser ablation technique (Liang et al. 2004). In
addition, doped anatase TiO2 nanoparticles were produced by the solution combus-
tion method (Nagaveni et al. 2004b). Nevertheless, the disadvantages of this method
are the high cost, low yield, and difficulty in managing the structure and morphol-
ogy of the nanomaterials.

2.2.2.5 Templating Method


The process to construct materials with a similar morphology is known as templat-
ing method. The production of nanomaterials which uses the templating method has
become exceptionally popular recently. This method uses the morphological char-
acteristics with reactive deposition, so it is possible to prepare numerous new mate-
rials with a regular and controlled morphology by simply changing the morphology
of the template materials. Over the past few years, a variety of templates have been
developed to synthesize different nanomaterials (Jinsoo et al. 2005; Iwasaki et al.
2004). This method has some shortcomings, like complicated synthetic procedures
where templates must be removed, normally by calcination technique, which causes
an increase in the manufacturing costs and also chances of contamination (Bavykin
et al. 2006).

2.2.2.6 Combustion Method


The combustion method includes a quick heating of a solution comprising redox
groups. This method leads to production of highly crystalline nanoparticles with
large surface areas (Nagaveni et al. 2004a, c). During production, the temperature
reaches to roughly 650°Celisus for 1–2 min to make the crystalline materials.

2.2.2.7 Gas Phase Method


This method is good to produce thin film because it can be performed chemically or
physically. Nanomaterials are formed because of chemical reaction or decomposi-
tion of a precursor in the gas phase (Jones et al. 2003; Lee et al. 2017). Moreover,
physical vapor deposition (PVD) is another technique which can be used to produce
thin film deposition. Interestingly, films are formed from the gas phase method
without using chemical transition. To produce TiO2 thin films, a beam of electrons
heats the TiO2 material and the electrons are produced and this process is recog-
nized as Electron beam (E-beam) evaporation. There are many benefits of making
of TiO2 deposited with E-beam evaporation than CVD method such as smoothness
and better conductivity (Van de Krol et al. 1997).

2.2.2.8 Microwave Radiation Method


Nanomaterials can also be produced by using microwave radiation and there are
several benefits of this method, like this method does not use high temperature
20 F. A. Khan

calcination for extended period of time and also is a quick method of making crys-
talline nanomaterials (Corradi et al. 2005). Moreover, high quality of rutile rods can
be created by joining hydrothermal and microwave methods, while TiO2 hollow
open-­ended nanotubes can be manufactured through reacting anatase and rutile
crystals in the NaOH solution (Wu et al. 2005).

2.2.2.9 Conventional Sol-Gel Method


This method has numerous advantages, for example, this method allows impregna-
tion or co-precipitation of nanomaterials, which can be used to introduce dopants.
To synthesize various oxide materials, sol-gel method has been used (Fernandez-­
Garcia et al. 2004), and this method allows better control for the texture formation,
the chemical reaction, and the morphological properties of the solid materials. The
major benefit of the Sol-Gel technique is the ability to scale up with a high purity of
nanomaterials (Kolen’ko et al. 2005). In Sol-Gel technique process, a colloidal sus-
pension is formed from the hydrolysis and polymerization reactions of the precur-
sors. These precursors are usually inorganic metal salts or metal organic compounds
(Pierre 1998). In addition, any factor that effects either or both reactions are likely
to impact the properties of the gel formation and these factors are generally described
as Sol-Gel technique factors. These factors include type of solvent, water content,
acid or base content, and different type of precursor, precursor concentration, and
temperature. These factors affect the structure of the initial gel formation. After this
step, the wet gel can be mature in another solvent. The time between the formation
of a gel and its drying is known as aging (Chen and Mao 2007).

References
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als: synthesis, properties, and applications. Adv Mater 18(21):2807–2824
Cao Y, Yang W, Zhang W, Liub G, Yue P (2004) Improved photocatalytic activity of Sn4þ doped
TiO2 nanoparticulate films prepared by plasma-enhanced chemical vapor deposition. New J
Chem 2(8):218–222
Carp O, Huisman CL, Reller A (2004) Photoinduced reactivity of titanium dioxide. Prog Solid
State Chem 32:33
Chen X, Mao SS (2007) Titanium dioxide nanomaterials: synthesis, properties, modifications, and
applications. Chem Rev 107:2891
Cheng H, Ma J, Zhao Z, Qi L (1995) Hydrothermal preparation of uniform nanosize rutile and
anatase particles. Chem Mater 7:663–671
Corradi AB, Bondioli F, Focher B, Ferrari AM, Grippo C, Mariani E, Villa C (2005) Conventional
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