nanobiotechnology and its applications in medical diagnostics and biomedical field 1
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Nanobiotechnology And Its Applications In
Medical Diagnostics And Biomedical Field.
Maninder Singh 818Mayank 820
Pranshu Abhishek 832
Sumit Gupta 847
Rajdeep Pal 8551
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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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IntroductionSize 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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WHAT IS NANOTECHNOLOGY?
* 1 millimeter = 1,000 micrometers;1 micrometer = 1,000 nanometersSource: "Nanotech: The Tiny Revolution" by CMPCientífica (November 2001)
Structures(e.g. materials)
Devices(e.g. sensors)
Systems(e.g. NEMS)
Nanotechnology isthe manipulation of matter at thenanometer* scale
to create novelstructures, devicesand systems.
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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
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Nano shirt, slacks, tie, tennis racket, odor/ bacteria eliminatingsocks, 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
Video Journey into NanotechnologyNational Cancer Institute, Alliance for Nanotechnology
in Cancer – http://nano.cancer.gov/resource_center/video_journey.asp
National Cancer Institute Video Journey Into Nanotechnology.flv
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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 beexpanded to include structures measured in
microns also.
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Present Major MedicalApplications
- Cardiovascular
- Drug delivery &Therapy
- Genetics
- Neurology
- Oncology
- Point of care diagnostics
- Surgery
- Tissue engineering- Prostheses
- Pathology
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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, animaltesting)
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Hot R&D Topics
• Lab on Chip
• Retinal Implants
• Non Invasive Blood GlucoseMonitoaring
• The ‘Electronic Rat’
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Timescales?
• Roadmaps based on– current status of R&D
– Future vision
– Past experience
• Balance market drivers againstbarriers
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Nano molecular diagnostics
Nano chips/bio chipsNano arrays/protein nanoarrays
Drug discoveryGene therapy and RNAinterference
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Method
Nano particle protein chip
Nano particles for molecular
diagnosticsNano 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 formolecular diagnostics
DNA protein and nano particle conjugates
Nanoparticle based colorimetric DNAdetection method
Nanobiosensors
Nanowirebiosensors etc
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Biobarcode assay for proteins
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Instrument for DNADetection
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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.
HandHeldmodel
Submersible
model
KinExA™model BenchTop
model
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NANOPLEX™ biomarkers are robust, patented opticaldetection labels that bring entirely new, much-needed
capabilities to clinical diagnostic and life sciencemeasurements.
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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 sensorsEnzymes
-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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Fib ti h l t l
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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 aspecific spots on a device.
Each spot includes thousands of to millions of copies
of a DNA strand
NANOARRAY
CHIP
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DNA-nanoparticle complexes
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•
DNA molecule
DNA-nanoparticlecomplexes basedon Au-thiolbinding
Nanoparticlelabeling for biochips
Labeling of singlemolecules
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
DendrimersDendrimers, 1- to 10-nanometer
spherical polymers of uniformmolecular weight made
from branched monomers (Poly
imido amine), are provingparticularly adept at providingmultifunctional modularity.
Dendrimers can serve as versatile
nanoscale platforms for creatingmultifunctional devices capableof detecting cancer and deliverydrugs.
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Nanotechnology in observing
disease processes involving fibrils
using AFM
growth of beta-amyloid (->Alzheimer !) visualized by AFM36
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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
vesiclesliposomes
micelles
polymerssolid 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 PLGAnanoparticles. Intense fluorescence indicates
deposition of nanoparticles in the arterial wall.
L=lumen, NP=nanoparticles, A= adventitia41
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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 adesired protein.
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Cell microencapsulation in polymer
matrix
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Enhanced Permeability and Retention
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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 PEGylatedParticles within the tumor site
•
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Nanotechnology and cancer
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Nanotechnology and cancer therapy
Silica coated lipid micelles
Silica-coated lipid
micelles containingLH-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
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Micellar Nano-particles in cancer therapy
Lymphatic delivery
Tumor conc. of 99mTc labelledEtoposide 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) 46
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Poly Butyl Cyanoacrylate nanoparticles
loaded with Dox
• Prepared by dispersionpolymerization in DextranMedia
• Particle size: 100-300 nm
• Entrapment : 86-90%• Tumor Conc. Of 99mTc-
Dox and 99mTc-DPBCNano-particles in Dalton’slymphoma 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 solidlipid nanoparticle
(SLN) production
leading to a drug
enriched shell
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Tumor accumulation Studies with
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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
3
2
1
0
1a 1b 2a 2b
Time (h)
3a 3b
a : ET
b : ETPL
1 : 1h2 : 6h
3 : 24h