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Nanobiotechnology And Its Applications In

Medical Diagnostics And Biomedical Field.

Maninder Singh 818


Mayank 820
Pranshu Abhishek 832
Sumit Gupta 847
Rajdeep Pal 8551
What is Nanobiotechnology?
Biotechnology is the application of technological
innovation as it pertains to biological and life sciences.

Nanobiotechnology incorporates biotechnology on the


nano-scale.

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Introduction
Size Ranges of Biological
Material
• Cells: 100um – 10um

• Cell organelles (nucleus,


mitochondrion): 10um –
1um

• Viruses: 100nm- 50nm

• Cell material (proteins,


lipids, DNA, RNA): 10nm –
0.1nm

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Introduction
Nanobiotechnology is an emerging field
• cells discovered 1665
• electron microscope 1950s
• Watson and Crick discover DNA double helix 1953
• Mapping of Human Genome 2003

Where is nanobiotechnology going? Applications?


• Cell structure and physiology
• Virus Detection
• Radiation/Chemotherapy
• Drug delivery
• Neurological functions of the brain
• Biomedical engineering research
• Study of molecular behavior
• Utilization of imaging devices

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WHAT IS NANOTECHNOLOGY?

Nanotechnology is
the manipulation of
matter at the
nanometer* scale
to create novel
structures, devices
and systems.

Structures Devices Systems


(e.g. materials) (e.g. sensors) (e.g. NEMS)

* 1 millimeter = 1,000 micrometers;


1 micrometer = 1,000 nanometers
Source: "Nanotech: The Tiny Revolution" by CMP
Científica (November 2001)

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Economic impact of
nanotechnology
Market Size Predictions
(within six years)
$340B/yr Materials
$300B/yr Electronics
$180B/yr Pharmaceuticals
$100B/yr Chemical manufacture
$ 70B/yr Aerospace
$ 20B/yr Tools
$ 30B/yr Improved healthcare
$ 45B/yr Sustainability

$1 Trillion, growing to $2.6 Trillion by 2014

*Estimates by industry groups, source: NSF and LUX


Nano shirt, slacks, tie, tennis racket, odor/ bacteria eliminating
socks, nano car wax, and 2004 Chevy Impala with nano enhanced
side panels.

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Nanobiotechnology In Medical
Technologies

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Nanotechnology in Health
Care

National Cancer Institute Video Journey Into Nanotechnology.flv

Video Journey into Nanotechnology


National Cancer Institute, Alliance for Nanotechnology
in Cancer – http://nano.cancer.gov/resource_center/video_journey.asp

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Nano-technology
Nanotechnology is a new field with many
possible uses, medicine being one of them.
Nanotech was first predicted by Nobel Laureate
Richard Feynman in 1959.
It’s anything to do with structures one to several
hundred nanometers long in at least one
direction. However, nanotechnology doesn’t
necessarily deal with nanometers, as it can be
expanded to include structures measured in
microns also.
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Present Major Medical
Applications

- Cardiovascular - Point of care diagnostics


- Surgery
- Drug delivery & - Tissue engineering
Therapy - Prostheses
Pathology
- Genetics -

- Neurology
- Oncology

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Size of Markets
• Drugs & Drug Delivery $80 billion
• Blood Analysis $22 billion
• Heart Pacemakers & $16 billion
Other Implants
• Endoscopy & MIS Tools $5 billion
• Hearing Aids $4 billion
• DNA / Lab on Chip $1.2 billion

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Drivers in healthcare
– Ageing population
– Personalized health
– Earlier diagnosis
– Cost of healthcare
– Global travel (epidemics)
– Food safety
– Monitoring of individuals (glucose,
cholesterol)
– Ethics (eg stem cell research, animal
testing)

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Hot R&D Topics
• Lab on Chip
• Retinal Implants
• Non Invasive Blood Glucose
Monitoaring
• The ‘Electronic Rat’

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Timescales?
• Roadmaps based on
– current status of R&D
– Future vision
– Past experience
• Balance market drivers against
barriers

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Nano molecular diagnostics

Nano chips/bio chips


Nano arrays/protein nano
arrays
Drug discovery
Gene therapy and RNA
interference
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Method

Nano particle protein chip


Nano particles for molecular
diagnostics
Nano arrays for molecular diagnostics
Nanotechnologies on biochips

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Lab-on-a-chip systems are miniaturized biosensors that,coupled with
portable instruments, promise to offer inexpensive, point of care
medical diagnosis. The technology is being tested for use in the
monitoring of HIV immune function.

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Lab-on-a-chip systems
 Study of chromosomes by AFM
 Application of nanopore technology for
molecular diagnostics
 DNA protein and nano particle conjugates
 Nanoparticle based colorimetric DNA
detection method
 Nanobiosensors
 Nanowirebiosensors etc

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Biobarcode assay for proteins

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Instrument for DNA
Detection

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Biosensors
These are the biosensors under development in world-class laboratories. Some
of these devices were developed in collaboration with PPP model.

 
     
            
                     

     

HandHeld Submersible
model model

KinExA™
model BenchTop
model
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NANOPLEX™ biomarkers are robust, patented optical
detection labels that bring entirely new, much-needed
capabilities to clinical diagnostic and life science
measurements.

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Nanotechnology based biosensor prototype capable

of species-specific detection of microorganisms

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Cantilever arrays QD

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Applications

Diagnostics Using Sensors and Nano


Electro Mechanical Systems (NEMS) &
implants
Drug Delivery Using Nanoparticles and
Molecular Carriers
Lab on a Chip and Advanced Drug
Delivery Systems

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Applications

Diagnostics Using Sensors and Nano


Electro Mechanical Systems (NEMS) &
Implants
Drug Delivery Using Nanoparticles and
Molecular Carriers
Lab on a Chip and Advanced Drug
Delivery Systems

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As diagnostics

• Biosensing

• Nanoarrays: genes and proteins

• Nanoparticle complexes of DNA and


peptides

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Biological recognition elements
for sensors
Enzymes
-transformation of analyte into sensor detectable product

Antibody-antigens
-high affinity binding with tracer to generate a signal

DNA-ligand binding

Biomimetic sensors
-engineered molecules (single chain antibody fragment)
- supported lipid bilayers
-molecularly imprinted polymers

Whole cells or cellular structures


-pollutant dependent inhibition/ activation of cell respiration
-membrane transport proteins
-neuroreceptor proteins produce signal through ion channels
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Fiber-optic cholesterol sensor

The enzyme cholesterol oxidase converts cholesterol


and oxygen to cholestenone and peroxide. The
change in oxygen is sensed by the decacyclene
fluorescence. B. Kuswandi et al., Analyst, 2001

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Nanoarrays
Nanoarray with single-stranded DNA representing
thousands of different genes, each assigned to a
specific spots on a device.

Each spot includes thousands of to millions of copies


of a DNA strand

NANOARR
AY
CHIP
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Protein arrays for diagnostics

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DNA-nanoparticle complexes

• DNA molecule
• DNA-nanoparticle
complexes based
on Au-thiol
binding
• Nanoparticle
labeling for
biochips
• Labeling of single
molecules
• Devices, e.g.
nanoelectronics.

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DNA-coated gold nanoparticles (NPs) system
that also uses larger magnetic microparticles (MMPs) to detect

at tomolar (10-18) concentrations of serum proteins .

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Nanotechnology and diagnostics
Dendrimers
Dendrimers, 1- to 10-nanometer
spherical polymers of uniform
molecular weight made
from branched monomers (Poly
imido amine), are proving
particularly adept at providing
multifunctional modularity.

Dendrimers can serve as versatile


nanoscale platforms for creating
multifunctional devices capable
of detecting cancer and delivery
drugs.

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Nanotechnology in observing
disease processes involving fibrils
using AFM

growth of beta-amyloid (->Alzheimer !) visualized by AFM


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Applications

Diagnostics Using Sensors and Nano


Electro Mechanical Systems (NEMS) &
Implants
Drug Delivery Using Nanoparticles and
Molecular Carriers
Lab on a Chip and Advanced Drug
Delivery Systems

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Drug encapsulation and delivery
with nanoparticles
vehicles for delivery
• coated solid particles
• vesicles
• liposomes
• micelles
• polymers
• solid lipid nanoparticles

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Nanoparticle as Delivery System for Drugs
or Genes for Tissue and Cell

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Intracellular trafficking of nanoparticles
Nanoparticles eventually act as intracellular
reservoirs for sustained release of
encapsulated therapeutic agent.

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Tissue targeting of nanoparticles

Cross section of pig coronary artery infused


with rhodamine B containing PLGA
nanoparticles. Intense fluorescence indicates
deposition of nanoparticles in the arterial wall.
L=lumen, NP=nanoparticles, A= adventitia
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Block copolymer micelles for gene
therapy
Transfection of
plasmid DNA using
diblock copolymer.

DNA is released inside


the cytosol and
appears in the
nucleus to express a
desired protein.

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Cell microencapsulation in polymer
matrix

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Enhanced Permeability and Retention
(EPR) effect)
Nanoparticle entry and accumulation in tumors
• PEGylated particles, in the desired size range, leaks out of the
microvasculature and accumulates into the tumor site.

• Insufficient lymphatic drainage favors retention of PEGylated


Particles within the tumor site

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Nanotechnology and cancer
therapy
Silica coated lipid micelles

Silica-coated lipid
micelles containing
LH-RH as a targeting
agent have been
used to deliver iron
oxide particles to LH-
RH receptor- positive
cancer cells
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Micellar Nano-particles in cancer therapy
Lymphatic delivery
Tumor conc. of 99mTc labelled
Etoposide and EPM 1, 6, 24
hours after S.C.Inj.
12
10
8
6
4
2
0

Time (h)

Admn. Of etaposide loaded polysorbate 20 micellar


formulation (Right bar) by S.C. Inj. Enhanced the
tumor uptake in comparison to etoposide (Left bar)
Ref: Reddy & Murthy (2005) Acta Pharm.(In Press)
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Poly Butyl Cyanoacrylate nanoparticles
loaded with Dox
• Prepared by dispersion
polymerization in Dextran
Media
• Particle size: 100-300 nm
• Entrapment : 86-90%
• Tumor Conc. Of 99mTc-
Dox and 99mTc-DPBC
Nano-particles in Dalton’s
lymphoma solid tumor
bearing mice
• Ref: Reddy & Murthy: J.
Drug Targeting, 12(7),
2004, 433-451
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Nanostructured lipid carriers

• Phase separation
process during
cooling in solid
lipid nanoparticle
(SLN) production
leading to a drug
enriched shell

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Tumor accumulation Studies with
Etoposide nanoparticles (ETPL)
• Tumor accumulation of 99mTc-Etoposide and 99mTc-
ETPL in Dalton’s lymphoma tumor bearing mice
• Radioactivity measured 1h, 6h and 24h after
subcutaneous administration
Ref: Reddy & Murthy:AAPS Journal, 6(3), Article 23, 2004

2 a : ET
b : ETPL
1 1 : 1h
2 : 6h
0
3 : 24h
1a 1b 2a 2b 3a 3b
Time (h)

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