Nanotechnology and animal health

Nanoparticles and Animal
Health
DOCTORAL SEMINAR
ABDULRAHMAN MOHAMMED
L-2012 -V-21-D
SCHOOL OF PUBLIC HEALTH & ZOONOSES

Nano:
Nanobots A prefix that means very,
Nano-
Nanometre
stuff
Nanotechnol
Nano-Produ
Nanomedicine
Nanoscience
very, small.
The word nano is from the Greek
word ‘Nanos’ meaning Dwarf. It is a
prefix used to describe "one billionth"
of something, or 0.000000001.

What is Nanotechnology?
 A disruptive technology, with a potential to change
the world as we know it today.
 Nanotechnology? It is the study of controlling
and manipulating matter on an atomic
and/or molecular scale.
 It deals with structures the size of 100
nanometers or smaller in at least one dimension.
 It’s a very diverse technology

Definitions
 A nanometer is a billionth of a meter.
 It’s difficult to imagine anything so small, think of something only 1/80,000
the width of a human hair.
 Ten hydrogen atoms could be laid side-by side in a single nanometer.
 Nanotechnology is the creation of useful materials, devices, and systems
through the manipulation of matter on this miniscule scale.
 The emerging field of nanotechnology involves scientists from many
different disciplines, including physicists, chemists, engineers, and
biologists.
 There are many interesting nano devices being developed that have a
potential to improve cancer detection, diagnosis, and treatment

National Nanotechnology Initiative
 The National Nanotechnology Initiative, a government initiative in
the USA describes nanotechnology as: ‘research and development
(R&D) aimed at understanding and working with – seeing,
measuring and manipulating – matter at the atomic, molecular and
supramolecular levels. This correlates to length scales of roughly 1 to
100 nanometres. At this scale, the physical, chemical and biological
properties ofmaterials differ fundamentally and often unexpectedly
from those of the corresponding bulk materials’.
 Nanotechnology, as a new enabling technology, has the potential to
revolutionise agriculture and food systems throughout the world.
Nanotechnology can provide new tools for molecular and cellular
biology and new materials for pathogen detection, so there are
several areas in which nanotechnology could be applied to the
science and engineering of agriculture and food systems, e.g.
agricultural and food systems security, disease treatment delivery
systems, and the protection of the environment

History of Nanotechnology
• ~ 2000 Years Ago – Sulfide nanocrystals used by Greeks and Romans to dye
hair
• ~ 1000 Years Ago (Middle Ages) – Gold nanoparticles of different sizes used
to produce different colors in stained glass windows
• 1974 – “Nanotechnology” - Taniguchi uses the term nanotechnology for the
first time
• 1981 – IBM develops Scanning Tunneling Microscope
• 1985 – “Buckyball” - Scientists at Rice University and University of Sussex
discover C60
• 1986 – “Engines of Creation” - First book on nanotechnology by K. Eric
Drexler. Atomic Force Microscope invented by Binnig, Quate and Gerbe
• 1989 – IBM logo made with individual atoms
• 1991 – Carbon nanotube discovered by S. Iijima
• 1999 – “Nanomedicine” – 1st nanomedicine book by R. Freitas
• 2000 – “National Nanotechnology Initiative” launched

A Brief History of Nanotechnology
 On December 29, 1959,
physicist Richard Feynman
gave a radical lecture at an
American Physical Society
meeting at Caltech titled
“There’s Plenty of Room at
the Bottom”.
 Feynman suggested that it should
be possible to make machines
at a nano-scale that "arrange
the atoms the way we want",
and do chemical synthesis by
mechanical manipulation.
 This lecture was the birth of the
idea and study of
nanotechnology.

Hibbs’s Idea on Nanotechnology in Medicine
 Albert R. Hibbs -a noted mathematician was fascinated by
self-actuated machines. According to Feynman,
Hibbs originally suggested to him (circa 1959) the
idea of a medical use for Feynman's theoretical
micromachines:
“A friend of mine (Albert R. Hibbs) suggests a very
interesting possibility for relatively small machines. He
says that… it would be interesting in surgery if
you could swallow the surgeon. You put the
mechanical surgeon inside the blood vessel and it
goes into the heart and ``looks'' around … It
finds out which valve is the faulty one and takes
a little knife and slices it out. Other small
machines might be permanently incorporated in
the body to assist some inadequately-functioning
organ”. – Richard Feynman, “There’s Plenty of Room at
the Bottom”.
 What Feynman and Hibbs considered a possibility,
today 51 years later, is becoming a reality.

Various Types of Nanomaterials
10
Anthropogenic or
Engineered NPs
Incidental Particles
from:
Natural Particles
from:
•Carbon-based
•Nanotubes,
•Fullerenes
•Metal Oxides
•Quantum Dots
•Nanotubes
•Nanowires
•Dendrimers
•Combustion products
•Industrial Processes
•Vehicles emissions
•Construction
•Plants, Trees
•Oceans, other
•water bodies
•Erosion
•Dust

Types of Nanoparticles
• Nanoparticles fall into three major types:
• Naturally occurring
• Incidental
• Engineered
• Naturally Occurring
• Examples of naturally occurring nanoparticles include:
• Sea spray
• Mineral composites
• Volcanic ash
• Viruses
• Incidental Nanoparticles
• A result of man-made industrial processes, incidental nanoparticles include:
• Cooking smoke
• Diesel exhaust
• Welding fumes
• Industrial effluents
• Sandblasting
• Engineered Nanoparticles
• Engineered nanoparticles comprise of any manufactured particles with nanoscale
dimensions. Examples include:
• Metals
• Quantum dots
• Buckyballs/nanotubes
• Sunscreen pigments
• Nanocapsules

The size of selected nanotechnology materials is
estimated to be as follows:
 Nanoparticles 1 – 100 nm
 Fullerene (C60) 1 nm
 Quantum Dot 8 nm
 Dendrimer 10 nm
Materials found in nature are typically referenced to
have the following dimensions:
 Atom 0.1 nm
 DNA (width) 2 nm
 Protein 5 – 50nm
 Virus 5 – 100nm
 Bacteria 1,000 – 10,000 nm
 White Blood Cell 10,000 nm

Creation of Nanoparticles
Two basic approaches for creating nanodevices.
Top-down approach
Bottom-up approach

Top-Down
 Milling processes: The
mechanical production approach
uses milling to crush
microparticles.
 This approach is applied in
producing metallic and ceramic
nanomaterials.
 For metallic nanoparticles, high-energy
ball mills are used. Such
mills are equipped with grinding
media composed of wolfram
carbide or steel

Bottom-up
 Vapour condensation: typically
used to make metallic oxide ceramic
nanoparticles.
 A solid metal is evaporated and is
then rapidly condensed to form
nanosized cluster that settle down in
form of powder.
 Or, the metal vapour is released into
a vacuum chamber which contains a
rotating drum coated with a thin
layer of viscose substance.
 Nanoparticles form in suspension in
the liquid coating on the drum.

Nanodevices Are Small Enough to Enter Cells
Most animal cells are 10,000 to 20,000 nanometers in diameter
 Nanoscale devices (less than 100 nm) can enter cells and the
organelles inside them to interact with DNA and proteins.
 Tools developed through nanotechnology may be able to detect
disease in a very small amount of cells or tissue.
 They may also be able to enter and monitor cells within a living
body.

Nanomaterials categories
 One dimension
 Less than 100nm
 Nanoscale layers
Eg. thin films or surface coatings like computer chips
 Two dimensions
 Nanowires and nanotubes
 Three dimensions
 Precipitates
 Colloids and Quantum dots (tiny particles of
semiconductor materials)

Nanoparticles preparation
 Nanoparticles prepared from such substances as
proteins, olysaccharides and synthetic polymers
 The selection of matrix materials is dependent on
a) Size of nanoparticles required
b) Inherent properties of the drug, e.g., aqueous
solubility and stability
c) Surface characteristics such as charge and
permeability
d) Degree of biodegradability, biocompatibility and
toxicity
e) Drug release profile desired
f) Antigenicity of the final product

Types of nanoparticles
 Nanomaterials are materials (either newly created throughnanotechnology or
that exist in nature) that provide the potential to manipulate structures or other
particles at the nanoscale and to control and catalyse chemical reactions.
 Materials are generally composed of particles of many sizes. The shape,
structure and aggregation of particles at the nanoscale influence the properties
of the material at the macro-level.
 Specific examples of nanomaterials are buckeyballs, dendrimers, nanoshells,
nanotubes and quantum dots.
 Liposomes, polymer nanoparticles (nanospheres and nanocapsules)
 Solid lipid nanoparticles, nanocrystals, polymer therapeutics such as
dendrimers, fullerenes (most common as C60 or buckyball, similar in size of
hormones and peptide a-helices)
 Inorganic nanoparticles (e.g. gold and magnetic nanoparticles)

Bucky balls (fullerenes)
 Fullerenes, a carbon allotrope
 The buckminster fullerene is the most common form of fullerene
 7 Å in diameter with 60 carbon atoms arranged in a shape known as
truncated icosahedrons
 It resembles a soccer ball with 20 hexagons and 12 pentagons
 Scientists (6) have discovered how to make the metal-filled buckeyballs
soluble, bringing them a step closer to biological applications, such as the
delivery of medicine or radioactive material to a disease site
The idea of using the 60-atom to 80-atom hollow
carbon molecules for drug delivery is what gives added
biological functionality to a buckeyball. The aim is to
attach water-soluble groups of peptides or hydrophilic
chains to get these molecules into the blood stream.

Nanotubes…
 Nanotubes - opened on two sides with additional atom groups added in the characteristic
hexagon shape to form a hollow carbon tube (cylinder)
 Sheet of graphite (a hexagonal lattice of carbon) rolled into a cylinder
 This nanotubes are used to tracking oestrus in animals - detect the estradiol antibody at the
time of oestrus by near infrared fluorescence
 Used in gene therapy
 Another nanodevice that will help identify DNA changes associated with cancer is the
nanotube.
 Nanotubes are carbon rods about half the diameter of a molecule of DNA that not only can
detect the presence of altered genes, but they may help researchers pinpoint the exact
location of those changes.
 To prepare DNA for nanotube analysis, scientists must attach a bulky molecule to regions
of the DNA that are associated with cancer. They can design tags that seek out speciÞc
mutations in the DNA and bind to them.

Dendrimers…
 Dendrimers are 3-D man-made nanomolecules with regular
branching structures
 The branches arise from the core in shape of a spherical
structure by means of polymerisation
 This results in formation of cavities within the dendrimer
molecule which can be used for drug transport
 The ends of the dendrimer molecule can be attached with
other molecules for transport

Quantom dots…
 A 2-10 nm nano-scale crystalline structure made from
cadmium selenide
 Re-emits the white light in a couple of nanoseconds -
specific color which can be made to fluoresce when
stimulated by light
 Their structure consists of an inorganic core, the size of
which determines the colour emitted, an inorganic shell
and an aqueous organic coating to which biomolecules are
conjugated
 These particles enable powerful new approaches to genetic
analysis, drug discovery, and disease diagnostics

…Quantom dots
 Quantum dots - emit light at any wavelength
 Inserted almost anywhere, including liquid solution,
dyes etc
 Quantum dots can be attached to a variety of surface
ligands, and inserted into a variety of organisms for
in-vivo research
 quantum dots respond to light- it may be possible to
illuminate the body with light and stimulate the
quantum dot to heat up sufficient to kill the
cancerous cell

Nano shells
 Dielectric (silica) core coated with an ultra-thin metallic
(gold), layer size ranging from 10-500 nm.
 Strong optical absorption.
 Optical response depends on size of the core and thickness of
the gold shell.
 Shows broad range of an optical spectrum.
Nanoshells are extremely small beads of glass coated
with gold. They can be fashioned to absorb light of
almost any wavelength, but nanoshells that capture
energy in the near-infrared, which can easily penetrate
several centimeters of tissue

Biosilicon
 Highly porous silicon based nanomaterial product, that can
release a medicine slowly over a period of time.
 First by Australian company Sivida ,they fashion tiny
capsules(to be swallowed) and also tiny needles that can be
built into patch to invisibly pierce the skin and deliver drugs.
 Monitor sugar level in the blood.

Viral nanoparticles
 Viruses including cowpea mosaic virus, cowpea chlorotic
mottle virus, canine parvovirus, and bacteriophages have been
used in tissue targeting and drug delivery.
 ligands or antibodies including transferrin, folic acid, and
single-chain antibodies have been conjugated to viruses for
specific tumor targeting in vivo.
( Manchester M et al 2006)
 canine parvovirus, have natural affinity
transferrin receptors that are up-regulated on a variety
of tumor cells. (Singh P et al. 2006)

Applications in Surgery
 With nanotechnology, minute surgical
instruments and robots can be made which can
be used to perform microsurgeries on any part
of the body.
 Instead of damaging a large amount of the body,
these instruments would be precise and
accurate, targeting only the area where surgery
should be done.
 Visualization of surgery can also be improved.
Instead of a surgeon holding the instrument,
computers can be used to control the nano-sized
surgical instruments. “Nanocameras” can
provide close up visualization of the surgery
 Less chance of any mistakes or faults
 Surgery could also be done on tissue,
genetic and cellular levels.

Applications in Medical Robotics
 Nano-robotics, although having
many applications in other areas,
have the most useful and variety of
uses in medical fields.
 Potential applications include early
diagnosis and targeted drug
delivery for cancer, biomedical
instrumentation, surgery,
pharmacokinetics, monitoring
of diabetes, and health care.
 Future medical nanotechnology
expected to employ nanorobots
injected into the patient to perform
treatment on a cellular level.

Drug delivery
By only targeting the afflicted cells, less of the drug is
needed, reducing the side effects and making the drug
less expensive.
As drug only needs to go to certain targets instead of
whole body, it works faster to relieve the patient.
 Smaller the drug–carrying unit, more it tends to
concentrate itself in inflamed areas.
 By using the nanobiotechnology ,drug delivery can be
accomplished by encapsulation of the drug inside a
membrane with channels that open and close
according to outside stimuli.

Applications in Drugs and Medicine
 Nanotechnology can deliver medicine or drugs into
specific parts of the human body, thereby making
them more effective and less harmful to the other
parts of the body.
 A recent study conducted by NIH found anti-cancer
gold nanoparticles very effective.
 Gold “nanoshells” are useful to fight cancer because
of their ability to absorb radiation at certain
wavelengths. Once the nanoshells enter tumor cells
and radiation treatment is applied, they absorb the
energy and heat up enough to kill the cancer cells.
 Not only gold but other elements can also be used.

Disease diagnosis and treatment
 Diagnosis and Imaging: Microchips labelled with human
molecules are designed to emit an electrical impulse signal when
the molecules detect signs of a disease.
 Special sensor nanobots cheap and portable.
 Inserted into the blood, check and warn of any possible desease.
 Quantum dots: bind themselves to proteins unique to cancer
cells, kill the cancer cells by exposing UV light.

Nanoshells:
injected into the
animal’s loodstream
with targeted agents.
 Attach to the surface
receptors of cancer
cells. Illumination of
the body with
infrared light raises
the cell temperature
to about 55°C, which
‘burns’ and kills the
tumour.

Cancer-battling nanoshells
The nanoshell has a gold exterior layer which covers interior
layers of silica and Drugs. It can release tumor- specific
antibodies when infrared light is administered

‘Smart’ superparamagnetic
nanoparticles:
• when injected in the bloodstream target
tumour receptor cells.
 made from iron oxides (5-100 nm), when
subjected to a magnetic field enhance the
ability of the nanoparticles to locate
tumour cells.
 At the site of the tumour the nanoparticles
emit an attached drug to kill the cancer
cells.

Gold nanoparticles: Shows intense color in
visible region for spectroscopic detection.
 Used in biological labeling and imaging.
 Can be prepared easily; low toxicity.
 Gold reflects red light at nanoscale,
thus it is used to kill the cancerous
cell with visible light without
harming the normal cells.
(Zahrov V P et al 2005)

Nanochips: employs the power of an electronic
current that separates DNA probes to specific
sites on the array based on charge and size.
 the test sample (blood) can be analyzed for target
DNA sequences by hybridization with these
probes.
 Hybridised DNA will fluoresce which is
detected an relayed back to an onboard system
through platinum wiring.

MEMS
 Methods of making micro-sized
machines or microelectromechanical systems
(MEMS) are already established.
 Fully functional pumps, rotors, sensors and
levers exist at the microscale.
 swallowed capsule technology pills that allow
doctors to visualize GI bleeding.
 “The patient swallows a capsule containing a
lightemitting diode for illumination, a CMOS
(complementary metal-oxide semiconductor)
video camera and optics for taking images, a
battery, and a transmitter”
 The images are then transmitted to a receiver
worn on the patient’s belt and the doctor is
then able to diagnose the cause of the
ailment.

Tissue reconstruction
Treatment of an Injured Bone:
 An ultrasound is performed on existing bone
structures and then bone-like nanoparticles are
created using the results of the ultrasound.
(Silva et al 2004).
 The bone-like nanoparticles (15-18 nm ceramic and
poly methyl methacrylate copolymer) are inserted into
the body in a paste form. (Adhikari et al
2005).
 When they arrive at the fractured bone, they assemble
themselves to form an ordered structure which later
becomes part of the bone. (Adhikari et al 2005).

Treatment of an injured nerves:
 Samuel Stupp and John Kessler at Northwestern
University in Chicago have made tiny rod like nano-fibers
called Amphiphiles.
 They are capped with amino acids and are known to
spur the growth of neurons and prevent scar tissue
formation.
(Wiess et al 2005)
 Artificial RBC’s: ultrathin polyethylene
glycolpolylacetic acid (PEG-PLA) membrane
containing Hb and enzymes.
(Chang et al 2009)

Applications to animal health
 Nanotechnology has opened up new vistas for applications in molecular
biology, biotechnology and almost all the disciplines of veterinary and animal
sciences.
 Excellence in animal health and production can be achieved by translation of
this newer technology to create effective services and products for animals.
 The ability to manufacture and manipulate matter on the nanoscale has
offered opportunities for application in diverse areas of animal sciences.
 Nanosensors, nanovaccines, adjuvants, gene delivery and smart drug delivery
methods have the potential to revolutionize animal health and production.
 There can be numerous applications of the nanomaterials for disease diagnosis,
treatment, drug delivery, animal nutrition, animal breeding, reproduction,
tissue engineering and value addition to animal products

Applications to animal health…
 “Smart” drug delivery system
 Disease diagnosis and treatment
 Gene therapy or DNA delivery
 Drugs discovery
 Nanovaccines and vaccine adjuvants
 Tissue repair
 Identity preservation and quality assurance
 Animal breeding and reproduction
 Animal nutrition
 Value added to animal products

Smart drug delivery system…
 The development of ‘smart’ treatment delivery systems on
the nanoscale uses similar concepts applied at the
molecular level.
 For example, ‘smart’ drug delivery systems in animals
would most likely contain small, sealed packages of the
drug to be delivered.
 The packages would not be opened until they reach the
desired location in the animal, e.g. the site of infection.

Advantages of Drug delivery system
 Time-controlled
 Spatially Targeted
 Self-regulated
 Remotely Regulated
 Pre-programmed

Antimicrobial property
 The silver nanoparticles show efficient antimicrobial
property compared to other salts
 Most effective on E.Coli, S.aureus, Klebsiella,
Pseudomonas
 The nanoparticles preferably attack the respiratory chain,
cell division finally leading to cell death
 The STEM (Scanning Transmission Electron
Microscopy) confirms the presence of silver in the cell
membrane and inside the bacteria
 Silver nanoparticles in most studies are suggested to be
non-toxic. But it suggested to be hazardous to the
environment (Braydich-Stolle et al., 2005)

Early detection of cancer…
 The current systems are limited by their selectivity
and efficiency to concentrate rare cells for molecular
assays
 Nanoscience can detect - circulating cancer cells,
which present often at 1–2 cells per milliliter of
blood.
 Combinatorial use of magnetic nanoparticles and
semiconductor QDs - increase the ability to capture
and evaluate these rare circulating cancer cells
 Bionanobarcodes, nanocantilevers, and nanowires
are promising technologies

Nanobarcode
 Cancer cells detection
 Protein and nucleic acid detection based on biobarcode-amplification
 Gold nanoparticles are modified with both target capture
strands and bar code strands that are subsequently
hybridized to bar code DNA, and magnetic microparticles
modified with target capture strands (BCA)
 Gold nanoparticles and the magnetic microbeads form
sandwich structures that are magnetically separated from
solution.
 Unhybridized bar code DNA are removed
 The bar codes (hundreds to thousands per target) are
detected by using a colorimetric method

Quantom dots on cancer detection…
 QD staining provides spatial localization information (both
inter- and intracellular),
 QD probes are delivered to tumors by both a passive
targeting mechanism and an active targeting mechanism
 In the passive mode, macromolecules and nanometer-sized
particles are accumulated preferentially at tumor sites
through the Enhanced permeability and retention
(EPR)effect.
 For active tumor targeting, Gao et al. used antibody
conjugated QDs to target a specific membrane antigen.

Imaging & therapy for tumors
Multifunctional nanoparticles for integrated cancer imaging and
therapy

Quantom dots on cancer detection…

Nanovaccines…
 Vaccines require immunostimulating compounds,
adjuvants, which act nonspecifically to increase the
immune response to a defined antigen
 Nanometer adjuvants are
1. Liposome
2. ISCOM based adjuvant
3. Biobullets
4. Virus like particles
 Nano-particles - 40–50 nm - potential to induce
potent cell mediated (CD4 and CD8 T cells) as well as
humoral immune responses

…Nanovaccines
 VLP vaccine against BT & AHS – strong protection
 ISCOM based vaccines effective on H5N1 in
chickens and EHV - 2 in horses
 Liposomes added vaccines protect the cattle
against BVDV
 Liposomes have also been used to deliver allergen
extracts as immunotherapy for refractory canine
atopic dermatitis
 “Biobullets” made of photopolymerized PEG
hydrogels can serve as biodegradable bullets used
to wild animals for vaccination. Eg. Bruella
abortus

Some of the proteins, polysaccharides
synthetic polymers and lipids used as
nanocarrier for drug delivery.

Nanoformulations against infectious organisms
tested for drug delivery in experimental animals with
potential for veterinary use. (Manuja eta l., 2012)

Nanovaccines/adjuvants against infectious organisms tested in
experimental animals with potential for veterinary use.
(Manuja et al., 2012)

Examples
 Disease diagnosis: A rapid, sensitive test has been developed for detection of
FMD virus which relies on the sensitivity and movement of liquid crystals at the
nanoscale in the presence of a target molecule. Virus binding in a detection
region is identified by changes in liquid crystal orientation.
 Therapeutics: the common antibiotic molecule gentamicin was bound to a
hydrogel using a peptide linker which can only be cleaved by a protease enzyme
formed by Pseudomonas aeruginosa; thus, the antibiotic is not released in
absence of the organism Proteases specific to particular bacteria can be used as
the signal for the release of different spectra of antibiotics from the same
matrix depending on the strain of bacterium.
 Animal nutrition: A nanocomposite of MgO-SiO2 has been used as an effective
adsorbing agent for removal of aflatoxin from wheat flour. Similarly, a modified
montmorillonite nanocomposite (MMN) has been used to reduce the toxicity
due to aflatoxin in feeds of broiler chicks.
 Value addition to animal products: Nanoparticles are being used to remove
Campylobacter and E. coli from poultry products. Listeria monocytogenes,
another foodborne pathogen was detected in spiked milk samples by magnetic
nanoparticle-based immune-magnetic separation combined with real-time
PCR.

Safety and toxicological issues
 Aggregates of nanoparticles are water soluble and kill useful
bacteria. (Balbus et al 2005).
 Nanoparticles are very light and can easily become airborne
and can cause asthma, bronchitis and can be fatal.
(Donaldson et al 2004).
 Nanoparticles flowing thorough the bloodstream may affect the
clotting system. (Donaldson et al 2004).
 May damage the brain and nervous system, could be fatal.
 Might move through a mother’s placenta to the foetus.
(Howard V 2004)
 Nanoparticles used in sunscreens created free radicals that
damage DNA.

Conclusions
 Nanotechnology is still in its early stages.
 As further research continues in this field, more treatments will
be discovered.
 Many diseases that do not have cures today may be cured by
nanotechnology in the future.
 If everything runs smoothly, nanotechnology will one day
become part of our everyday life and will help save many lives.

“Any intelligent fool can make things bigger, more
complex and more violent. It takes a genius- and a
lot of courage- to move in the opposite direction.”-
Albert Einstein
THANK YOU FOR
YOUR ATTENTION

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