INTRODUCTION TO NANOTECHNOLOGY

Basic principles of nanoscience and nanotechnology

Mohd Zobir Hussein

Programme Leader for Nanomaterials
Materials Synthesis and Characterization Laboratory (MSCL)
Institute of Advanced Technology (ITMA)
UNIVERSITI PUTRA MALAYSIA

(mzobir@upm.edu.my)

Visiting Professor, 3 in 1 Programme 2019, 30 Sept-4 Oct 2019, Fakultas Kedoktoran Gigi, UBI
 Content
• Introduction
• Examples of nanomaterials
• Nanoscale
• Theory
• Opportunities and challenges
• Applications
• Risks
• Classification of nanomaterials
• Nanomedicines; drug and theranostics nanodelivery systems
• Commercialised nanomedicines: nanodrugs
• Nanodelivery system: Design, synthesis and characterisation
• Supramolecular chemistry; host-guest and applications
• Advantages of nanomedicine
• Controlled release properties of drug
• Some examples of nanomaterials
 INTRODUCTION
Green plants convert more energy and synthesize a
greater tonnage of fine chemicals than the combined
global chemical industry. This is an example of
amazing nanobiotechnology process (Drexler, 1999)

High performance teeth in human (Risnes, 1998),

strong shells of shellfish are as a result of smart
and complex bionanotechnology processes
(Lin and Meyers, 2005).
Example of nanocomposite material: teeth
Example of nanocomposite material:
Layered Nanohybrid Materials
Paua abalone
Example of nanocomposite material:
Layered Nanohybrid Materials
Paua abalone
Nanoscale - a dimension of fascinating properties

Nano = dwaft (Greek)

1 nm = 1 x 10-9 m
=10 atoms
1Å = 1 x 10-10 m
Nanoscience and nanotechnology
 Nanoscience and nanotechnology

Nanoscience is the study of phenomena and manipulation of materials at

atomic, molecular and macromolecular scales, where properties differ
significantly from those at a larger scale.

Nanotechnology is the design, characterisation, production and application

of structures, devices and systems by controlling shape and size at
nanometer scale:~ (0.2–100) nm
(where unique phenomena enable novel applications)

Encompassing nanoscience, engineering and technology, nanotechnology

involves imaging, measuring, modeling and manipulating matter at this length
scale.
(The Royal Society 2004)
Nanoscience and nanotechnology

Nanoscience is concerned with understanding these effects and

their influence on the properties of materials

Nanotechnology aims to exploit these effects to create structures,

devices and systems with novel properties and functions due to
their ultra small size (nm)

Nanomedicines:
The use of nanoscience and nanotechnology for medicine (applications, processes, etc.)

Nanodrug delivery systems

Nanodiagnostic
Nanotheranostics
Multifunctional Nanotheranostics
Multimodal Nanotheranostics
Nanodentistry
etc.
 Nanomaterials

Nanomaterial and nanobiomaterial

size: 0.2 - 100 nm

At nanometer size regime

Larger surface area
Chemically more reactive
Has quantum size effects
electrical
magnetic
optical
 Nanoscale - a dimension of fascinating properties

At the nanoscale regime,

materials exhibit unusual and attractive properties;
ü lower resistance to electricity
ü lower melting points and
ü faster chemical reactions

Their extremely small size allows;

direct interaction with enzymes, proteins, DNA and other biomolecules,
opening great possibilities for
ü drug delivery
ü gene therapy
ü medical diagnostics
ü etc.
Gold nanoparticles showing the change in optical properties as a function of size
Nanoscience/Nanotechnology - a multidisciplinary approach
Opportunities/Challanges

NANOMEDICINE
Nanomedicine - a multidisciplinary approach
(Opportunities/Challenges)
 Application of
nanomaterials for
different areas
Application of graphene and CNTs for nanomedicines
Current and emerging applications of
nanomaterials for nanomedicine
THE OPPORTUNITIES TO CONTRIBUTE TO
NANOSCIENCE/NANOTECHNOLOGY

§ Synthesis of Nanostructures: new materials/nanostructures for new

discovery of new phenomena and novel applications.

§ Materials: the invention and development of materials whose properties

depend on nanoscale structure, which ultimately, be important in producing
these materials reproducibly, economically, and in quantity.

§ Molecular Mechanisms in Nanobiotechnology: By understanding the

molecular mechanisms of functional nanostructures in biology-the light-
harvesting apparatus of plants, ATPases, the ribosome, the structures that
package DNA-Physical and analytical chemistry will help to build the tools
that define these structures.

§ Risk Assessment and Evaluation of Safety: Understanding the risks of

nanostructures and nanomaterials will require cooperation across
disciplines that range from chemistry to physiology, and from molecular
medicine to epidemiology.
THE INDUSTRY OPPORTUNITIES

1) Tools for Research: To produce new tools and equipment for research (Instruments for
nanoscience/nanotechnology).
2) New Materials: Nanomaterials for electrically/magnetically/optically functional polymers,
particles, and composites for a range of applications, from spray-painted automobile
bumpers and nanoscale bar-coded rods, to the printed organic electronics of electronic
newspapers and smart shipping labels.
3) New Processes for Fabrication: The development of new processes to make new
nanomaterials at affordable cost.
4) Nanoelectronics: The development of new fabricating method with the sub-50-nm
dimensions required by nanoelectronics will present immediate opportunities for materials
science and chemistry.
5) Nanoparticle Technology: Specialized kinds of nanoparticles will become important in a
wide range of applications—from drugs to improve bioavailability, to electrodes and
lumiphores for new kinds of graphic displays, etc.
6) The Revolutionary Unknown: A final class—and the one that is the most exciting—
comprises the revolutionary ideas, for example, nano-CDs (read by an array of parallel
atomic force microscope tips known as the “centipede”), quantum computers, and
biocompatible nanoparticles able to reach, recognize, and report presymptomatic disease.
RISKS OF NANOTECHNOLOGY
A new technology sparks conflict between those wishing to exploit it as
rapidly as possible and those wishing to wait — to have it proved
absolutely safe.

Nanotechnology is new; although parts of it are quite familiar, parts are

unfamiliar, and it is not a surprise that the public is wary of its potential for
harm, as well as excited by its potential for good.

Therefore, Risk Assessment and Evaluation of Safety is important

Standard? MSDS, etc.

AND REMEMBER

Nanoscience is now an important, central thread in fundamental research, and it

will soon become an important part of technology.

In our enthusiasm for “nano”, we must not forget “micro”,

For many applications, microtechnology is more important than nanotechnology.

For example, assay systems based on mammalian cells for use in developing
drugs, nanotechnology NEEDS microworld: a mammalian cell is an object that is
a few micrometers (not nanometers) in size.

Research and development must be focused on the development of science and

technology at the right size—and that size may range from nanometers to
millimeters (for the technologies of small things): “nano” is not always the best or
only answer.

Nanoscience is now a thread woven into many fields of science.

Nanotechnology—certainly evolutionary, and perhaps revolutionary—will emerge
from it.
Classification approach
 Classification (dimension) - Siegel

The dimensionality and shape play a major role in determining the

characteristics of nanomaterials; physical, chemical and biological
characteristics.

Size ↓, → surface-to-volume ratio ↑

The smaller size of the nanomaterials give higher surface area.

Raman and FTIR spectroscopy (vibrational spectroscopy) are also based on

shapes
Classification (dimension) - Siegel

0D 1D 2D 3D
Carbon nanomaterials/allotrope

nanodiamond Graphene  graphite ionsdaleite

Fullerene- C60 Fullerene- C540 Fullerene=- C70

MWNT

Carbon nanospheres

Amorphous/activated carbon SWNT Carbon Nano Fibers

0D NANOMATERIALS

fullerene

QD

Basel = selasih = kemangi?

 1D NANOMATERIALS

CNF

CNT SWNT
 2D NANOMATERIALS

2D layered structure: ZLH, LDH, etc

Graphene, graphene oxide
3D NANOMATERIALS

activated carbon with 3D pores

NANOMATERIALS

3D
3
0D
0

2D
2 1D
1
 Carbon nanomaterials/allotrope

a) 0 D b) 2 D  3D c) 3 D

nanodiamond Graphene  graphite ionsdaleite

d) 0 D e) 0 D f) 0 D

Fullerene- C60 Fullerene- C540 Fullerene=- C70

g) 3 D
MWNT

Carbon nanospheres

Amorphous/activated carbon SWNT h) 1 D Carbon Nano Fibers

NANOMEDICINE

Is the application of nanotechnology in medicine (US NNI)

Science and technology, diagnostic, treatment and prevention of diseases and

injuries leading to pain relief, preserving and improving human health using
tools and molecular level knowledge of the human body
(Europe Science Foundation)

Generally nanomedicine is a comprehensive monitoring, management, repair,

protection and improvement of all human biological systems, operating at the
molecular level – and this purposely created using nanodevices and
nanostructures, ultimately leading to improve health status of individuals.

Caruana, BioMedical Physics, University of Malta

• Doxil (pegylated liposomal doxorubicin) – the 1st FDA approved (1995)
nanodrug - used to treat cancers; ovarian cancer and AIDS-related Kaposi's
sarcoma.

• To improve the balance between the efficacy and toxicity of doxorubicin

therapy.
 Nanodelivery system (NDS)

refers to approaches, formulations, technologies and systems for transporting

active agents (pharmaceutical/target/diagnostic/energy,etc.) to achieve its desired
effect using nanotechnology platform

Nanodelivery provides a means to control

a) stability
b) solubility
c) bioavailability,
d) controlled release properties.
 Nanodelivery System (NDS)

Advantage of NDS
the compatibility of nanoparticle properties with the properties of the bioactive
and the desired applications.

Physicochemical properties of nanoparticles such as

size, charge, hydrophobicity, and targeting molecules affect the absorption,
distribution, metabolism and excretion (ADME) of NDS.

The fate of the bioactive depends on its physicochemical properties

and the location of its release.

The safety of NDS is largely unknown.

Toxicological studies consisting of a combination of in silico, in vitro, and in vivo
are needed to reveal the safety of NDS for successful applications.
Design, synthesis and charaterisations of host-guest
materials for nanodelivery systems (NDS)

Factors
1) The physico-chemical properties of the host and the guest
2) The final desired tailor-made physico-chemical properties to be exploited
3) The interaction (bonding) of the host and the guest
for the formation of pure-phase nanomaterials
4) Method of synthesis to get pure-phase
5) Physico-chemical characterisations
 Supramolecular Chemistry

Supra (Latin) = above or beyond

•Chemistry beyond the molecules
•Chemistry of tailor-shape intermolecular interaction

Supramolecular Chemistry
The chemistry of the intermolecular bond
covering the structures and functions of the entities formed by the
association of  2 chemical species (J.M. Lehn)

The chemistry based upon intermolecular interactions (the association of  2

building blocks which are held together by intermolecular bonds (F. Vogtle)

Supramolecules
•Information is stored in the form of structural uniqueness
•The combined action and characteristic parts of the design component
molecules resulted in new properties or synergistic effect
 INTRODUCTION
Supramolecular Chemistry

v One of the fastest growing areas

in parallel with the nanotechnology era – bottom up approach
v Interdisciplinary field
v One of the fields is host-guest chemistry
 Host-guest

GUEST
(active agent)

+
HOST GUEST
HOST
(inorganic) (active agent)
(inorganic)

Method of synthesis = f(host-guest chemistry) – TYPE OF BONDS

Intercalation, encapsulation, dispersion, adsorption, conjugation, etc.
 INTRODUCTION

Type of interaction E KJ/Mol strength

Ion-ion 100 - 350 strongest
Ion-dipole 50 - 200
Dipole-dipole 5 - 50
H-bonding 4 - 120
p-systems 0 - 50
Van der Walls forces 5
Close packing
hydrophobic weakest

The supramolecular chemistry: has had a profound effect on structures

of different sizes and shapes especially for nanomaterials (1 to 100 nm)
 INTRODUCTION
Host-guest chemistry

A molecule (host) and another molecule (guest) can bind together

to produce a “host-guest” complex via noncovalent bond

Host possesses convergent binding site

Guest possesses divergent binding site

Host/Guest
A monoatomic cation
A simple inorganic anion
A complex molecule such as hormones, drugs, DNA, etc
 INTRODUCTION
Host-guest Chemistry

+ -

Electrostatic interaction = Complex

Molecular inclusion = Cavitand

Host Guest

Crystal lattice inclusion = Clathrand

 INTRODUCTION
Classification of supramolecular host-guest compounds

Interaction between the host and the guest

a) Electrostatic  the host-guest system is a complex

b) Nondirectional, less specific such as hydrophobic, VDW or crystal

close-packing then

i) Cavitand = host with intramoleular cavities

Host-guest aggregate is cavitate

ii) Clathrand = host with extramolecular cavities

Host-guest aggregate is clathrate
 INTRODUCTION
Application of host-guest nanomaterials

Sensors
Molecular recognition
Synthesis: di- and poly-merization, etc.
Separation and Purification
Organic Electronics
Crystal Engineering
Solar Energy
Polymers
Hydrogels for Soft Nanotechnology
Proteins and Nucleic Acids Targeting
Magnetic Resonance Imaging and Contrast Agents
Food and Textile Industries
Drug and Theranostic Delivery Systems
Energy
etc.
 INTRODUCTION
Application a) Dimerization/polymerization
 INTRODUCTION
Application b) molecular recognition
 Design, synthesis and characterisation of
drug/theranostic nanodelivery systems

APPLICATIONS GUEST HOST

DESIGN f=(active agent) (active agent) (nanomaterial)
drug 0D
diagnostic 1D
target 2D
Synthesis
method photothermal 3D
etc.
characterisations

Parametric GUEST
optimisation (active agent)
Pure phase
HOST
(nanomaterial)
Methods: f = (host-guest chemistry)
Intercalation, encapsulation, dispersion, adsorption, conjugation, etc.
 Design, synthesis and characterisations of NDS

Target tailor-made
properties Selection of the
host and the guest Host-guest
interaction
Synthesis
methods
TARGET
APPLICATION Therapeutic DS
STUDIES Diagnostic DS Parametric
Theranostic DS optimization
Multimodal DS
etc.
Phase-pure Physico-Chemical
product characterisations
 Design of drug delivery systems
(2D nanomaterials - by intercalation process)

Active agents

therapeutic ( )
Layered 2D nanomaterial Active agents-intercalated
nanomaterial (NDDS)
 Design of theranostics delivery system
(by intercalation + adsorption)

Active agents

therapeutic ( )
Layered nanomaterial
diagnostic ( ) Therapeutic and
eg. imaging probe
diagnostic active agents-
loaded nanomaterial
(TDS)
 Design of multifunctional theranostics delivery system (MTDS)
(by intercalationn + adsorption + conjugation)

Active agents

therapeutic ( )
Layered nanomaterial
diagnostic ( ) Active agents-loaded
Eg. imaging probe
nanomaterial (MTDS)
Target agent ( )
 Theranostics
Multifunctional nanodelivery
theranostics system
nanodelivery system (MTDS)
 DRUGS – as guests

Sun
protection
ANTI-
CANCER

ANTI-
HISTAMINE
CNS/ etc.
BBB

ANTI-TB
ANTI-
MICROBIAL
Advantages of NDS with controlled release property

Prevent harmful side-effects Toxic side effects

Increase compliancy

Tailor-made property (> 2 drugs) Controlled-release capability

Therapeutic window

Minimize drug degradation & loss Ineffective level

Advantages of NANOMEDICINE
 NANOEMULSION

2D LAYERED NANOHYBRID POLYMER NANOPARTICLE

NDS
LYPOSOME NANOPARTICLE
MAGNETIC NANOPARTICLE

CNSs Graphene,
GO, GQD,
etc.

AND MANY MORE

Carbon Nanostructures (CNS)
 Carbon nanomaterials/allotrope

a) 0 D b) 2 D  3D c) 3 D

nanodiamond Graphene  graphite ionsdaleite

d) 0 D e) 0 D f) 0 D

Fullerene- C60 Fullerene- C540 Fullerene=- C70

g) 3 D
MWNT

Carbon nanospheres

Amorphous/activated carbon SWNT h) 1 D Carbon Nano Fibers

Carbon Nanotubes (CNTs)
 Carbon Nanotubes (CNTs)

Some Important Properties

i) Metallic, semi-conducting or superconducting
ii) The largest elastic modulus of any material ever known.
iii) The hollow structure - able to store guest molecules
(such as Lithium)
iv) Functional groups can be generated to anchor biological
materials or drugs, etc. for transportation to the target
Carbon Nanotubes (CNTs)
CNT for multifunctional biomedical application

Imaging probe

Targeting moiety
Therapeutic molecule
GRAPHENE
ü One of the thinnest and strongest materials
ü 2D sheet of carbon just one atom thick
ü ‘honeycomb’ structure
ü 100 times stronger than steel
ü highly conductive and flexible

The Nobel Prize in Physics for 2010 was awarded to

Andre Geim and Konstantin Novoselov, for
groundbreaking experiments for the 2D material.
 GRAPHENE OXIDE (GO)
Ø Is the most important derivatives of graphene
Ø contains many oxygenated functional groups:
(hydroxyls, epoxides and carboxylic acids) - confer on the tremendous
biocompatibility, water solubility)
Ø Has dual-characteristics (hydrophilic edges and hydrophobic basal plane)
Ø high surface area ~ 2600 m2/g.
Ø All of these characteristics are ideal for drug delivery applications.

Ref. Nano Lett. 2010, 10, 4328–4334., ). Nano Lett. 2009, 9, 2654–2660, Science 2006, 313, 951–954, Nat Nanotechnol 2008;3:101-5, J
Mater Chem 2010:3448-54, J Am Chem Soc: 2010;132(23):8180–6.
Preparation of GO

stirred for 12 hrs

at 50 °C,
sonication &
work up

[Marcano et al. ACS VOL. 4 ▪ NO. 8 ▪ 4806–4814 ▪ 2010]

 XRD Analysis
G raphite Flakes
3.7 Å
intensity/cps

Graphene oxide
9.0 Å

10 20 30 40
2ϴ/degrees
 Graphite

INH-GO
GO
GRAPHENE QUANTUM DOTS

F. Liu, et al., Adv. Mater.,

2013, 25 3657
F. Liu, et al., Adv. Mater., 2013, 25 3657
Kim, et al., ACS Nano, 2012, 6(9) 8203-8208
 Green GQD

Synthesis of strongly green-photoluminescent graphene quantum dots for drug carrier,

Wang, et al., Coll. Surf Sc., Coll Surf B: Biointerface 2013, 112 192-196.
 Green GQD

Synthesis of strongly green-photoluminescent graphene quantum dots for drug carrier,

Wang, et al., Coll. Surf Sc., Coll Surf B: Biointerface 2013, 112 192-196.
Application of nanotechnology for dentistry (nanodentistry)
 CONCLUSIONS

Nanotechnology based on nanoscience is multidiciplinary studies.

Nanomaterials show fascinating properties compared to their bulk
counterparts. They show promising opportunities and challenges
beside their possible risks.

Various types of nanomaterials with different dimensions; 0, 1, 2 and

3D can be designed to be used for nanomedicine especially as
multifunctional delivery systems for various drugs, target and imaging
agents. This can be extended for dentistry or NANODENTISTRY.
 Take home keywords

• Examples of nanomaterials
• Nanomaterials and their properties
• Opportunities and challenges
• Applications and risks
• Classification of nanomaterials
• Nanomedicine for drug and theranostics nanodelivery systems
• Commercialised nanomedicines: nanodrugs
• Nanodelivery system: Design, synthesis and characterisation
• Supramolecular chemistry; host-guest and their applications
• Advantages of nanomedicine, controlled release properties
• Specific examples of nanomaterials: CNTs, graphenes and their derivatives.