Mohd Zobir HusseinProgramme 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

INTRODUCTION TO NANOTECHNOLOGYBasic principles of nanoscience and nanotechnology

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

1 Å = 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 systemsNanodiagnosticNanotheranosticsMultifunctional NanotheranosticsMultimodal NanotheranosticsNanodentistryetc.

Nanomaterials

Nanomaterial and nanobiomaterialsize: 0.2 - 100 nm

At nanometer size regimeLarger surface areaChemically more reactiveHas quantum size effects

electricalmagnetic optical

Nanoscale - a dimension of fascinating properties

At the nanoscale regime,materials exhibit unusual and attractive properties; ü lower resistance to electricityü 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 deliveryü gene therapyü medical diagnosticsü etc.

Gold nanoparticles showing the change in optical properties as a function of size

NANOMEDICINE

Nanoscience/Nanotechnology - a multidisciplinary approachOpportunities/Challanges

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 NANOTECHNOLOGYA 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

0 D 1 D 2 D 3 D

Carbon nanomaterials/allotrope

nanodiamond Graphene graphite ionsdaleite

Fullerene- C60 Fullerene- C540 Fullerene=- C70

Amorphous/activated carbon SWNT

MWNT

Carbon nanospheres

Carbon Nano Fibers

0D NANOMATERIALS

Basel = selasih = kemangi?

QD

fullerene

1D NANOMATERIALS

SWNTCNT

CNF

2D NANOMATERIALS

2D layered structure: ZLH, LDH, etcGraphene, graphene oxide

3D NANOMATERIALS

activated carbon with 3D pores

NANOMATERIALS

2

0

1

3 0D

1D2D

3D

Carbon nanomaterials/allotrope

nanodiamond Graphene graphite ionsdaleite

Fullerene- C60 Fullerene- C540 Fullerene=- C70

Amorphous/activated carbon SWNT

MWNT

Carbon nanospheres

Carbon Nano Fibers

a) 0 D

g) 3 D

h) 1 D

b) 2 D 3D c) 3 D

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

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)

Factors1) 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 nanomaterials4) Method of synthesis to get pure-phase5) Physico-chemical characterisations

Supra (Latin) = above or beyond•Chemistry beyond the molecules•Chemistry of tailor-shape intermolecular interaction

Supramolecular ChemistryThe chemistry of the intermolecular bondcovering the structures and functions of the entit ies 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

Supramolecular Chemistry

INTRODUCTIONSupramolecular Chemistry

v One of the fastest growing areas in parallel with the nanotechnology era – bottom up approach v Interdisciplinary fieldv One of the fields is host-guest chemistry

Host-guest

Method of synthesis = f(host-guest chemistry) – TYPE OF BONDSIntercalation, encapsulation, dispersion, adsorption, conjugation, etc.

HOST(inorganic)

GUEST(active agent) HOST

(inorganic)

GUEST(active agent)

+

INTRODUCTION

Type of interaction E KJ/Mol strengthIon-ion 100 - 350 strongestIon-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)

INTRODUCTIONHost-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 siteGuest possesses divergent binding site

Host/Guest A monoatomic cationA simple inorganic anionA complex molecule such as hormones, drugs, DNA, etc

INTRODUCTIONHost-guest Chemistry

Host Guest

Crystal lattice inclusion = Clathrand

Molecular inclusion = Cavitand

Electrostatic interaction = Complex

+ -

INTRODUCTIONClassification 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

INTRODUCTIONApplication of host-guest nanomaterials

SensorsMolecular recognitionSynthesis: di- and poly-merization, etc.Separation and PurificationOrganic ElectronicsCrystal EngineeringSolar Energy PolymersHydrogels for Soft NanotechnologyProteins and Nucleic Acids TargetingMagnetic Resonance Imaging and Contrast AgentsFood and Textile IndustriesDrug and Theranostic Delivery SystemsEnergyetc.

INTRODUCTIONApplication a) Dimerization/polymerization

INTRODUCTIONApplication b) molecular recognition

Design, synthesis and characterisation of drug/theranostic nanodelivery systems

Methods: f = (host-guest chemistry)Intercalation, encapsulation, dispersion, adsorption, conjugation, etc.

DESIGNAPPLICATIONSf=(active agent)

HOST(nanomaterial)

GUEST(active agent)

Synthesismethod

Parametric optimisation

characterisations

Pure phase

HOST(nanomaterial)

GUEST(active agent)

drug

diagnostic

targetphotothermal

etc.

0D1D2D3D

Design, synthesis and characterisations of NDS

Target tailor-made properties

Synthesis methods

Parametric optimization

Phase-pureproduct

Physico-Chemical characterisations

TARGET APPLICATION

STUDIESTherapeutic DSDiagnostic DS

Theranostic DSMultimodal DS

etc.

Selection of the host and the guest Host-guest

interaction

Design of drug delivery systems(2D nanomaterials - by intercalation process)

Active agents-intercalated nanomaterial (NDDS)

Layered 2D nanomaterial

Active agents

therapeutic ( )

Design of theranostics delivery system (by intercalation + adsorption)

Therapeutic and diagnostic active agents-

loaded nanomaterial (TDS)

Layered nanomaterial

Active agents

therapeutic ( ) diagnostic ( )

eg. imaging probe

Design of multifunctional theranostics delivery system (MTDS) (by intercalationn + adsorption + conjugation)

Active agents-loaded nanomaterial (MTDS)

Layered nanomaterial

Active agents

therapeutic ( ) diagnostic ( )

Eg. imaging probe

Target agent ( )

Theranostics nanodelivery systemMultifunctional theranostics nanodelivery system (MTDS)

DRUGS – as guests

ANTI-CANCER

CNS/BBB

ANTI-HISTAMINE

ANTI-MICROBIAL

ANTI-TB

Sun protection

etc.

Advantages of NDS with controlled release property

Prevent harmful side-effects

Controlled-release capability

Therapeutic window

Toxic side effects

Ineffective levelMinimize drug degradation & loss

Increase compliancy

Tailor-made property (> 2 drugs)

Advantages of NANOMEDICINE

NDS

NANOEMULSION

2D LAYERED NANOHYBRID POLYMER NANOPARTICLE

MAGNETIC NANOPARTICLELYPOSOME NANOPARTICLE

CNSs Graphene, GO, GQD,

etc.

AND MANY MORE

Carbon Nanostructures (CNS)

Carbon nanomaterials/allotrope

nanodiamond Graphene graphite ionsdaleite

Fullerene- C60 Fullerene- C540 Fullerene=- C70

Amorphous/activated carbon SWNT

MWNT

Carbon nanospheres

Carbon Nano Fibers

a) 0 D

g) 3 D

h) 1 D

b) 2 D 3D c) 3 D

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

Carbon Nanotubes (CNTs)

Carbon Nanotubes (CNTs)

Some Important Propertiesi) 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

Therapeutic molecule

Imaging probe

Targeting moiety

ü One of the thinnest and strongest materialsü 2D sheet of carbon just one atom thickü ‘honeycomb’ structure ü 100 times stronger than steelü highly conductive and flexible

GRAPHENE

The Nobel Prize in Physics for 2010 was awarded to Andre Geim and Konstantin Novoselov, for groundbreaking experiments for the 2D material.

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.

GRAPHENE OXIDE (GO)

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

10 20 30 40

Graphite Flakes

Graphene oxide

2ϴ/degrees

9.0 Å

3.7 Å

inte

nsity

/cps

Graphite

GO INH-GO

F. Liu, et al., Adv. Mater.,2013, 25 3657

GRAPHENE QUANTUM DOTS

F. Liu, et al., Adv. Mater., 2013, 25 3657

Kim, et al., ACS Nano, 2012, 6(9) 8203-8208

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.

Green GQD

Application of nanotechnology for dentistry (nanodentistry)

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.

CONCLUSIONS

• 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.

Take home keywords