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NANOTECHNOLOGY

ITS ROLE IN CANCER DIAGNOSIS AND
            TREATMENT
Objectives
 Should be able to give definition for
  Nanotechnology.
 Understand how the potential of Nanotechnology
  is harnessed in cancer. This includes its role in
   Prevention and Control of Cancer
   Early Detection and Proteomics
   Imaging Diagnostics
   Multifunctional Therapeutic


  o The Advantages of Using Nanotechnology for
   cancer treatment.
Properties of Cancer Cells
 Epidermal Growth Factor Receptor (EGFR) over
  expression and over activity have been
  associated many different types of Cancer
 Cancer cells have a unique properties that can be
  exploited by nanoparticles.
 Their rapid rate of growth causes them to intake
  an abnormal amount of nutrients (i.e., folic acid)
 Nanoparticles can be used to target bio-markers
  or antigens that are highly specific to Cancer
  cells.
What is Nanotechnology
 The design, characterization, production, and
 application of structures, devices, and
 systems by controlled manipulation of size
 and shape at the nanometer scale
 (atomic, molecular, and macromolecular
 scale) that produces structures, devices, and
 systems with at least one novel/superior
 characteristic or property
 There are many interesting nanodevices being
 developed that have a potential to improve
 cancer detection, diagnosis, and treatment.
Nanotechnology Plays by different rules
 Nanoscale research is designed to reach a better understanding of how matter
behaves on this small scale.
 The factors that govern larger systems do not necessarily apply at the nanoscale.
Because nanomaterials have large surface areas relative to their
volumes, phenomena like friction and sticking are more important than they are in
 There are two basic approaches for creating
 nanodevices. Scientists refer to these methods
 as:
   The top-down approach
   The bottom-up approach.
 The top-down approach involves molding or
  etching materials into smaller components.
 The bottom-up approach involves assembling
  structures atom- by-atom or molecule-by-
  molecule, and may prove useful in manufacturing
  devices used in medicine.
Designing Nanodevices for Use in the Body
Nanodevices Are Small Enough to Enter Cells
Most animal cells are 10,000 to 20,000 nanometers in diameter. This means that nanoscale
devices (less than 100 nanometers) 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.
Cancer detection using
nanotechnological devices
Nanodevices Can Improve Sensitivity
In order to successfully detect cancer at its earliest stages, scientists must
be able to detect molecular changes even when they occur only in a
small percentage of cells. This means the necessary tools must be
extremely sensitive. The potential for nanostructures to enter and analyze
single cells suggests they could meet this need.
Nanodevices Can Improve Cancer Detection and
                     Diagnosis
Detection of cancer at early stages is a critical step in improving cancer treatment.
Currently, detection and diagnosis of cancer usually depend on changes in cells and tissues
that are detected by a doctor’s physical touch or imaging expertise.
Instead, scientists would like to make it possible to detect the earliest molecular
changes, long before a physical exam or imaging technology is effective. To do this, they
Nanodevices Can Preserve Patients’ samPles

This is important because the samples clinicians use to screen for cancer are often in limited
supply.
It is also important because it can capture and preserve cells in their active state. Scientists would
like to perform tests without altering cells, so the cells can be used again if further tests are needed.
Nanodevices Can Make Cancer Tests Faster and More
                    Efficient
DNA-coated gold nanoparticles (NPs) form the basis of a system that also uses larger magnetic
micro particles (MMPs) to detect attomolar (10-18) concentrations of serum proteins. In this
case, a monoclonal antibody to prostate specific antigen (PSA) is attached to the MMP, creating a
reagent to capture free PSA. A second antibody to PSA, attached to the NPs, is then
added, creating a “sandwich” of the captured protein and two particles that is easily separated
using a magnetic field.
Cantilevers Can Make Cancer Tests
    Faster and More Efficient
 One nanodevice that can improve cancer detection
 and diagnosis is the:
   Cantilever:These tiny levers, which are anchored at one
    end, can be engineered to bind to molecules that
    represent some of the changes associated with cancer.
    They may bind to altered DNA sequences or proteins
    that are present in certain types of cancer. When these
    molecules bind to the cantilevers, surface tension
    changes, causing the cantilevers to bend. By monitoring
    the bending of the cantilevers, scientists can tell whether
    molecules are present.
   Scientists hope this property will prove effective when
    cancer-associated molecules are present--even in very
    low concentrations--making cantilevers a potential tool
    for detecting cancer in its early stages.
Nanopore
 Scientists believe nanopores, tiny holes that allow
 DNA to pass through one strand at a time, will
 make DNA sequencing more efficient.
  As DNA passes through a nanopore, scientists can
   monitor the shape and electrical properties of each
   base, or letter, on the strand. Because these
   properties are unique for each of the four bases that
   make up the genetic code, scientists can use the
   passage of DNA through a nanopore to decipher
   the encoded information, including errors in the
   code known to be associated with cancer.
Nanopores
Nanotubes- marking Mutations
nanotube
 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 specific mutations in the
 DNA and bind to them.
Nanotubes — Mapping Mutations
Nanotubes — Mapping
            Mutations
 Once the mutation has been tagged, researchers
  use a nanotube tip resembling the needle on a
  record player to trace the physical shape of DNA
  and pinpoint the mutated regions.
 The nanotube creates a map showing the shape
  of the DNA molecule, including the tags
  identifying important mutations.
 Since the location of mutations can influence the
  effects they have on a cell, these techniques will
  be important in predicting disease.
Quantum dots
 Another minuscule molecule that will be used to
  detect cancer is a quantum dot. Quantum dots are
  tiny crystals that glow when they are stimulated by
  ultraviolet light.
 The wavelength, or color, of the light depends on the
  size of the crystal.
 Latex beads filled with these crystals can be
  designed to bind to specific DNA sequences. By
  combining different sized quantum dots within a single
  bead, scientists can create probes that release
  distinct colors and intensities of light.
 When the crystals are stimulated by UV light, each
  bead emits light that serves as a sort of spectral bar
  code, identifying a particular region of DNA.
Quantum Dots Can Find Cancer Signatures
Quantum Dots Can Find Cancer Signatures
Quantum Dots Can Find Cancer Signatures


 To detect cancer, scientists can design quantum dots
  that bind to sequences of DNA that are associated
  with the disease.
 When the quantum dots are stimulated with light,
  they emit their unique bar codes, or labels, making
  the critical, cancer-associated DNA sequences visible.
 The diversity of quantum dots will allow scientists to
  create many unique labels, which can identify
  numerous regions of DNA simultaneously.
 This will be important in the detection of cancer,
  which results from the accumulation of many different
  changes within a cell.
 Another advantage of quantum dots is that they can
  be used in the body, eliminating the need for biopsy.
NANOTECHNOLOGY AND CANCER
        THERAPY
Advantage of nanotechnology
        treatment
 Nanoscale devices have the potential to radically
  change cancer therapy for the better and to
  dramatically increase the number of highly
  effective therapeutic agents
 Should serve as customizable, targeted drug
  delivery vehicles capable of ferrying large doses
  of chemotherapeutic agents or therapeutic genes
  into malignant cells while sparing healthy cells,
  which would greatly reduce or eliminate the often
  unpalatable side effects that accompany many
  current cancer therapies
Continued..



 Nanotechnology may also be useful for
  developing ways to eradicate cancer cells without
  harming healthy, neighboring cells.
 Scientists hope to use nanotechnology to create
  therapeutic agents that target specific cells and
  deliver their toxin in a controlled, time-released
  manner.
Disadvantages
 Cancer targeting is highly dependent on surface
    chemistry. Not just any nanoparticle will work.
   The need for biocompatible and stable
    nanoparticles
   Side-effects and toxicity
   Environmental impact
   Uncharted territory
Improving Cancer Treatment
The use of Dendrimers
 spherical, branched polymers that are silica-
  coated micelles, ceramic nanoparticles, and
  cross-linked liposomes, can be targeted to cancer
  cell.
 This is done by attaching monoclonal antibodies
  or cell-surface receptor ligands that bind
  specifically to molecules found on the surfaces of
  cancer cells.
   such as the high-afinity folate receptor and
   luteinizing hormone releasing hormone (LH-RH)
   or molecules unique to endothelial cells that
   become co-opted by malignant cells
  The nanoparticles are rapidly taken into cells
Structures of biocompatible dendrimers that have been tested for drug delivery
applications. (a) PAMAM dendrimer. (b) Polyaryl ether dendrimer. (c) Polylysine
dendron. (d) Polyester dendrimer based on glycerol and succinic acid.
Nanoshells

 Nanoshells are miniscule beads coated with
  gold. By manipulating the thickness of the layers
  making up the nanoshells, scientists can design
  these beads to absorb specific wavelengths of
  light.
 The most useful nanoshells are those that absorb
  near-infrared light, which can easily penetrate
  several centimeters of human tissue.
 The absorption of light by the nanoshells creates
  an intense heat that is lethal to cells.
Nanoshells as Cancer Therapy
Researchers can
already link nanoshells
to antibodies that
recognize cancer cells.
Scientists envision
letting these
nanoshells seek out
their cancerous
targets, then applying
near-infrared light.
 In laboratory
cultures, the heat
generated by the light-
absorbing nanoshells
has successfully killed
tumor cells while
 Experiment on mice bearing human prostate
    tumors
   After approximately 3 months
   100% of the mice treated with the targeted
    nanoparticles survived
   57% of the mice treated with untargeted
    nanoparticles survived
   14% of the mice with Docetaxel alone survived
   Amount of weight loss and white blood cell count
    confirmed far lower toxicity for the targeted
    nanoparticles
conclusion
 -Different types of Cancer cells have unique
  properties that can be exploited by nanoparticles
  to target the Cancer cells
 -Nanoparticles can be used to detect/monitor (by
  utilizing or adding optic, magnetic, and
  fluorescent properties) and to treat Cancer (by
  Heat ablation, chemotherapy, gene therapy).
 -No human trials have been performed yet and
  human trials are still at least a few years away.
  (Unknown side effects, toxicity, difficulty in
  manufacturing and harmful byproducts, need for
  highly specific nanoparticles

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Nanotechnology and potential in Cancer therapy and treatment

  • 1. NANOTECHNOLOGY ITS ROLE IN CANCER DIAGNOSIS AND TREATMENT
  • 2. Objectives  Should be able to give definition for Nanotechnology.  Understand how the potential of Nanotechnology is harnessed in cancer. This includes its role in  Prevention and Control of Cancer  Early Detection and Proteomics  Imaging Diagnostics  Multifunctional Therapeutic o The Advantages of Using Nanotechnology for cancer treatment.
  • 3. Properties of Cancer Cells  Epidermal Growth Factor Receptor (EGFR) over expression and over activity have been associated many different types of Cancer  Cancer cells have a unique properties that can be exploited by nanoparticles.  Their rapid rate of growth causes them to intake an abnormal amount of nutrients (i.e., folic acid)  Nanoparticles can be used to target bio-markers or antigens that are highly specific to Cancer cells.
  • 4. What is Nanotechnology  The design, characterization, production, and application of structures, devices, and systems by controlled manipulation of size and shape at the nanometer scale (atomic, molecular, and macromolecular scale) that produces structures, devices, and systems with at least one novel/superior characteristic or property
  • 5.
  • 6.  There are many interesting nanodevices being developed that have a potential to improve cancer detection, diagnosis, and treatment.
  • 7. Nanotechnology Plays by different rules  Nanoscale research is designed to reach a better understanding of how matter behaves on this small scale.  The factors that govern larger systems do not necessarily apply at the nanoscale. Because nanomaterials have large surface areas relative to their volumes, phenomena like friction and sticking are more important than they are in
  • 8.  There are two basic approaches for creating nanodevices. Scientists refer to these methods as:  The top-down approach  The bottom-up approach.  The top-down approach involves molding or etching materials into smaller components.  The bottom-up approach involves assembling structures atom- by-atom or molecule-by- molecule, and may prove useful in manufacturing devices used in medicine.
  • 9. Designing Nanodevices for Use in the Body
  • 10. Nanodevices Are Small Enough to Enter Cells Most animal cells are 10,000 to 20,000 nanometers in diameter. This means that nanoscale devices (less than 100 nanometers) 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.
  • 12. Nanodevices Can Improve Sensitivity In order to successfully detect cancer at its earliest stages, scientists must be able to detect molecular changes even when they occur only in a small percentage of cells. This means the necessary tools must be extremely sensitive. The potential for nanostructures to enter and analyze single cells suggests they could meet this need.
  • 13. Nanodevices Can Improve Cancer Detection and Diagnosis Detection of cancer at early stages is a critical step in improving cancer treatment. Currently, detection and diagnosis of cancer usually depend on changes in cells and tissues that are detected by a doctor’s physical touch or imaging expertise. Instead, scientists would like to make it possible to detect the earliest molecular changes, long before a physical exam or imaging technology is effective. To do this, they
  • 14. Nanodevices Can Preserve Patients’ samPles This is important because the samples clinicians use to screen for cancer are often in limited supply. It is also important because it can capture and preserve cells in their active state. Scientists would like to perform tests without altering cells, so the cells can be used again if further tests are needed.
  • 15. Nanodevices Can Make Cancer Tests Faster and More Efficient DNA-coated gold nanoparticles (NPs) form the basis of a system that also uses larger magnetic micro particles (MMPs) to detect attomolar (10-18) concentrations of serum proteins. In this case, a monoclonal antibody to prostate specific antigen (PSA) is attached to the MMP, creating a reagent to capture free PSA. A second antibody to PSA, attached to the NPs, is then added, creating a “sandwich” of the captured protein and two particles that is easily separated using a magnetic field.
  • 16. Cantilevers Can Make Cancer Tests Faster and More Efficient
  • 17.  One nanodevice that can improve cancer detection and diagnosis is the:  Cantilever:These tiny levers, which are anchored at one end, can be engineered to bind to molecules that represent some of the changes associated with cancer. They may bind to altered DNA sequences or proteins that are present in certain types of cancer. When these molecules bind to the cantilevers, surface tension changes, causing the cantilevers to bend. By monitoring the bending of the cantilevers, scientists can tell whether molecules are present.  Scientists hope this property will prove effective when cancer-associated molecules are present--even in very low concentrations--making cantilevers a potential tool for detecting cancer in its early stages.
  • 18. Nanopore  Scientists believe nanopores, tiny holes that allow DNA to pass through one strand at a time, will make DNA sequencing more efficient. As DNA passes through a nanopore, scientists can monitor the shape and electrical properties of each base, or letter, on the strand. Because these properties are unique for each of the four bases that make up the genetic code, scientists can use the passage of DNA through a nanopore to decipher the encoded information, including errors in the code known to be associated with cancer.
  • 21. nanotube  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 specific mutations in the DNA and bind to them.
  • 23. Nanotubes — Mapping Mutations  Once the mutation has been tagged, researchers use a nanotube tip resembling the needle on a record player to trace the physical shape of DNA and pinpoint the mutated regions.  The nanotube creates a map showing the shape of the DNA molecule, including the tags identifying important mutations.  Since the location of mutations can influence the effects they have on a cell, these techniques will be important in predicting disease.
  • 24. Quantum dots  Another minuscule molecule that will be used to detect cancer is a quantum dot. Quantum dots are tiny crystals that glow when they are stimulated by ultraviolet light.  The wavelength, or color, of the light depends on the size of the crystal.  Latex beads filled with these crystals can be designed to bind to specific DNA sequences. By combining different sized quantum dots within a single bead, scientists can create probes that release distinct colors and intensities of light.  When the crystals are stimulated by UV light, each bead emits light that serves as a sort of spectral bar code, identifying a particular region of DNA.
  • 25. Quantum Dots Can Find Cancer Signatures
  • 26. Quantum Dots Can Find Cancer Signatures
  • 27. Quantum Dots Can Find Cancer Signatures  To detect cancer, scientists can design quantum dots that bind to sequences of DNA that are associated with the disease.  When the quantum dots are stimulated with light, they emit their unique bar codes, or labels, making the critical, cancer-associated DNA sequences visible.  The diversity of quantum dots will allow scientists to create many unique labels, which can identify numerous regions of DNA simultaneously.  This will be important in the detection of cancer, which results from the accumulation of many different changes within a cell.  Another advantage of quantum dots is that they can be used in the body, eliminating the need for biopsy.
  • 29. Advantage of nanotechnology treatment  Nanoscale devices have the potential to radically change cancer therapy for the better and to dramatically increase the number of highly effective therapeutic agents  Should serve as customizable, targeted drug delivery vehicles capable of ferrying large doses of chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells, which would greatly reduce or eliminate the often unpalatable side effects that accompany many current cancer therapies
  • 30. Continued..  Nanotechnology may also be useful for developing ways to eradicate cancer cells without harming healthy, neighboring cells.  Scientists hope to use nanotechnology to create therapeutic agents that target specific cells and deliver their toxin in a controlled, time-released manner.
  • 31. Disadvantages  Cancer targeting is highly dependent on surface chemistry. Not just any nanoparticle will work.  The need for biocompatible and stable nanoparticles  Side-effects and toxicity  Environmental impact  Uncharted territory
  • 33. The use of Dendrimers  spherical, branched polymers that are silica- coated micelles, ceramic nanoparticles, and cross-linked liposomes, can be targeted to cancer cell.  This is done by attaching monoclonal antibodies or cell-surface receptor ligands that bind specifically to molecules found on the surfaces of cancer cells.  such as the high-afinity folate receptor and luteinizing hormone releasing hormone (LH-RH)  or molecules unique to endothelial cells that become co-opted by malignant cells The nanoparticles are rapidly taken into cells
  • 34. Structures of biocompatible dendrimers that have been tested for drug delivery applications. (a) PAMAM dendrimer. (b) Polyaryl ether dendrimer. (c) Polylysine dendron. (d) Polyester dendrimer based on glycerol and succinic acid.
  • 35.
  • 36. Nanoshells  Nanoshells are miniscule beads coated with gold. By manipulating the thickness of the layers making up the nanoshells, scientists can design these beads to absorb specific wavelengths of light.  The most useful nanoshells are those that absorb near-infrared light, which can easily penetrate several centimeters of human tissue.  The absorption of light by the nanoshells creates an intense heat that is lethal to cells.
  • 37.
  • 38. Nanoshells as Cancer Therapy Researchers can already link nanoshells to antibodies that recognize cancer cells. Scientists envision letting these nanoshells seek out their cancerous targets, then applying near-infrared light.  In laboratory cultures, the heat generated by the light- absorbing nanoshells has successfully killed tumor cells while
  • 39.  Experiment on mice bearing human prostate tumors  After approximately 3 months  100% of the mice treated with the targeted nanoparticles survived  57% of the mice treated with untargeted nanoparticles survived  14% of the mice with Docetaxel alone survived  Amount of weight loss and white blood cell count confirmed far lower toxicity for the targeted nanoparticles
  • 40. conclusion  -Different types of Cancer cells have unique properties that can be exploited by nanoparticles to target the Cancer cells  -Nanoparticles can be used to detect/monitor (by utilizing or adding optic, magnetic, and fluorescent properties) and to treat Cancer (by Heat ablation, chemotherapy, gene therapy).  -No human trials have been performed yet and human trials are still at least a few years away. (Unknown side effects, toxicity, difficulty in manufacturing and harmful byproducts, need for highly specific nanoparticles