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REVOLUTION IN TREATMENT OF CANCER

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Title: REVOLUTION IN TREATMENT OF CANCER


1
REVOLUTION IN TREATMENT OF CANCER
  • BY
  • NANOTECHNOLOGY

2
  • POSTER PRESENTED BY -
  • MAYANK RATHORE
  • SCHOOL OF STUDIES IN
    PHARMACEUTICAL SCIENCES
  • JIWAJI UNIVERSITY
  • GWALIOR (M .P.)
  • mayank_rathore2003_at_yahoo.co.in
  • Poster awarded 2nd prize by Department of
    Biotechnology and MPCST Cell of Jiwaji University
    (Govt. of India)
  • Venue - Department of Neurosciences
  • Jiwaji University Gwalior
  • Held on 28th February on occasion of
  • World Science Day
  • Having a theme Emerging Horizon of Sciences.

3
Nano technology
  • In ancient Greek Nano means dwarf. 
  • Nano technology is the creation of useful
    materials, devices and systems through the
    manipulation of mini scale matter (including
    anything with at least one dimension less than
    100 nanometers).
  • The emerging field of nano technology involves
    scientists from many different disciplines,
    including physicists, chemists, engineers and
    biologists R. P. Feynman, a physicist, initially
    used the Nanoscale.

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  • Tiny man-made nanoparticles have been used to
    successfully smuggle a powerful cancer drug into
    tumor cells leaving healthy cells unharmed.
  • When tested in mice, the Nan structure-based
    therapy was 10 times as effective at delaying
    tumor growth and far less toxic than the drug
    given alone.
  • Researchers believe the therapy could transform
    many cancers from killer into chronic, treatable
    diseases.
  • The major goals in designing nanoparticles as a
    delivery system are to control particle size,
    surface properties and release of
    pharmacologically active agents in order to
    achieve the site-specific action of the drug at
    the therapeutically optimal rate and dose
    regimen.

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  • The purpose of the chemotherapy and radiation is
    to kill the tumor cells as these cells are more
    susceptible to the actions of these drugs and
    methods because of their growth at a much faster
    rate than healthy cells, at least in adults.
  • Research efforts to improve chemotherapy over the
    past 25 years have led to an improvement in
    patient survival but there is still a need for
    improvement.

9
  • Current research areas include development of
    carriers to allow alternative dosing routes, new
    therapeutic targets such as blood vessels fueling
    tumor growth and targeted therapeutics that are
    more specific in their activity. Several nano
    biotechnologies mostly based on nanoparticles,
    have been used to facilitate drug delivery in
    cancer.
  • The magic of nanoparticles mesmerizes everyone
    because of their multifunctional character and
    they have given us hope for the recovery from
    this disease.
  • Although we are practicing better drug delivery
    paths into the body, we ultimately seek more
    accurate protocols to eradicate cancer from our
    society.  This review will primarily address new
    methods for delivering drugs, both old and new,
    with a focus on nano particle formulations and
    ones that specifically target tumors.

10
Core features of cancer cells-
  • Abnormal growth control
  • Improved cell survival
  • Abnormal differentiation
  • Unlimited replicated potential
  • Host tumor symbiosis

11
The Vision for Nano particles in the Treatment of
Cancer
  • Nano technology is the creation and utilization
    of materials, devices, and systems through the
    control of matter on the nanometer-length scale,
    i.e. at the level of atoms, molecules, and
    supramolecular structures.
  • These technologies have been applied to improve
    drug delivery and to overcome some of the
    problems of drug delivery for cancer treatment.
    Several nanobiotechnologies mostly based on
    Nanoparticles, have been used to facilitate drug
    delivery in cancer.

12
  • The magic of Nan particles mesmerizes everyone
    because of their multifunctional character and
    they have given us hope for the recovery from
    this disease.
  • Although we are practicing better drug delivery
    paths into the body, we ultimately seek more
    accurate protocols to eradicate cancer from our
    society. This review focuses on progress in
    treatment of cancer through delivery of
    anticancer agents via Nanoparticles. In addition,
    it pays attention to development of different
    types of Nanoparticles for cancer drug delivery.

13
Drug therapy of cancer treatment-
  • Transport of an anticancer drug in interestium
    (target cell) will be governed by physiological
    (i.e. pressure) and physiochemical (i.e.
    composition ,structure charge) property of
    target cell.
  • Also by physiochemical properties of molecules
    (size, configuration, charge and hydrophobicity)
    itself.

14
  • Thus to deliver therapeutic agent to tumour cell
    in vivo one must overcome the following
    problems-
  • Drug resistance at the tumor level due to
    physiochemical barrier (non cellular based
    mechanism).
  • Drug resistance at the cellular level (cellular
    mechanism).
  • Distribution, biotransformation clearance of
    anticancer drugs in the body.
  • A strategy could be associate antitumor drug with
    colloidal nanoparticles,with the aim to overcome
    noncellular and cellular based mechanism of
    resistance
  • to increase the selectivity of drugs toward
    cancer cells while reducing their toxicity toward
    normal cells.

15
Drug delivery strategies used to fight cancers-
  • Direct introduction of anticancer drugs into
    tumour
  • Injection directly into the tumour.
  • Tumour necrosis therapy.
  • Injection into the arterial blood supply of
    cancer.
  • Local injection into tumour for radio
    potentiation.
  • Localized delivery of anticancer drugs by
    electro-chemotherapy.
  • Local delivery by anticancer drug implants.

16
Routes of drug delivery
  1. Intraperitoneal
  2. Intrathecal
  3. Nasal
  4. Pulmonary inhalation
  5. Subcutaneous injection or implant
  6. Transdermal drug delivery
  7. Vascular route intravenous ,intra-arterial.

17
Systemic delivery targeted to tumour
  • Heat-activated targeted drug delivery .
  • Tissue-selective drug delivery for cancer using
    carrier-mediated transport systems .
  • Tumour-activated prodrug therapy for targeted
    delivery of chemotherapy .
  • Pressure-induced filtration of drug across
    vessels to tumour .
  • Promoting selective permeation of the anticancer
    agent into the tumour .
  • Two-step targeting using bispecific antibody .
  • Site-specific delivery and light-activation of
    anticancer proteins .

18
Drug delivery targeted to blood vessels of tumors
  1. Antiangiogenesis therapy .
  2. Angiolytic therapy .
  3. Drugs to induce clotting in blood vessels of
    tumour .
  4. Vascular targeting agents .

19
Special formulations and carriers of anticancer
drugs
  • Albumin based drug carriers
  • Carbohydrate-enhanced chemotherapy
  • Delivery of proteins and peptides for cancer
    therapy
  • Fatty acids as targeting vectors linked to active
    drugs
  • Microspheres
  • Monoclonal antibodies
  • Nanoparticles
  • Pegylated liposomes (enclosed in a polyethylene
    glycol bilayer)
  • Polyethylene glycol (PEG) technology
  • Single-chain antigen-binding technology

20
Transmembrane drug delivery to intracellular
targets
  • Cytoporter
  • Receptor-mediated endocytosis
  • Transduction of proteins and Peptides
  • Vitamins as carriers for anticancer agents

21
Biological Therapies
  • Antisense therapy
  • Cell therapy
  • Gene therapy
  • Genetically modified bacteria
  • Oncolytic viruses
  • RNA interference

22
Pathways For Nanoparticles In Cancer Drug
Delivery
  • Nanotechnology has tremendous potential to make
    an important contribution in cancer prevention,
    detection, diagnosis, imaging and treatment.
  • It can target a tumor, carry imaging capability
    to document the presence of tumor, sense
    pathophysiological defects in tumor cells,
    deliver therapeutic genes or drugs based on tumor
    characteristics, respond to external triggers to
    release the agent and document the tumor response
    and identify residual tumor cells.

23
  • Nanoparticles are important because of their
    nanoscaled structure but nanoparticles in cancer
    are still bigger than many anticancer drugs.
  • Their large size can make it difficult for them
    to evade organs such as the liver, spleen, and
    lungs, which are constantly clearing foreign
    materials from the body. In addition, they must
    be able to take advantage of subtle differences
    in cells to distinguish between normal and
    cancerous tissues.

24
  • Indeed, it is only recently that researchers have
    begun to successfully engineer nanoparticles that
    can effectively evade the immune system and
    actively target tumors. Active tumor targeting of
    nanoparticles involves attaching molecules, known
    collectively as ligands to the outsides of
    nanoparticles.
  • These ligands are special in that they can
    recognize and bind to complementary molecules, or
    receptors, found on the surface of tumor cells.
    When such targeting molecules are added to a drug
    delivery nanoparticle, more of the anticancer
    drug finds and enters the tumor cell, increasing
    the efficacy of the treatment and reducing toxic
    effects on surrounding normal tissues.

25
Development And Commercialization Of
Nanomaterials
  • Drug delivery techniques were established to
    deliver or control the amount, rate and,
    sometimes location of a drug in the body to
    optimize its therapeutic effect, convenience and
    dose. Combining a well established drug
    formulation with a new delivery system is a
    relatively low risk activity and can be used to
    enhance a companys product portfolio by
    extending the drugs commercial life-cycle.
  • Most companies are developing pharmaceutical
    applications, mainly for drug delivery. Most
    major and established pharmaceutical companies
    have internal research programs on drug delivery
    that are on formulations or dispersions
    containing components down to nano sizes.
  • With the total global investment in
    nanotechnologies currently at 5 billion, the
    global market is estimated to reach over 1
    trillion by 2011-2015. Nano and Micro
    technologies are part of the latest advanced
    solutions and new paradigm for decreasing the
    discovery and development time for new drugs and
    potentially reducing the development costs. 

26
Tools Of Nanotechnology
  • Some of the tools of nanotechnology having
    applications in cancer treatment are the
    following
  • Cantilevers
  • Nanopores
  • Nanotubes
  • Quantum dotes
  • Nanoshells
  • Dendrimers
  • Nanoboms
  • Nanowires
  • Nanoparticles
  • Gold nano-shells

27
1.Cantilevers
  • Tiny bars anchored at one end can be engineered
    to bind to molecules associated with cancer.
    These molecules may bind to altered DNA proteins
    that are present in certain types of cancer
    monitoring the bending of cantilevers it would
    be possible to tell whether the cancer molecules
    are present and hence detect early molecular
    events in the development of.

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2.Nanopores
  • Nanopores (holes) allow DNA to pass through one
    strand at a time and hence DNA sequencing can be
    made more efficient. Thus the shape and
    electrical properties of each base on the strand
    can be monitored. As these properties are unique
    for each of the four bases that make up the
    genetic code, the passage of DNA through a nano
    pore can be used to decipher the encoded
    information, including errors in the code known
    to be associated with cancer.

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3.Nanotubes
  • Nanotubes are smaller than Nanopores. Nanotubes
    carbon rods, about half the diameter of a
    molecule of DNA, will also help identify DNA
    changes associated with. It helps to exactly pin
    point location of the changes. Mutated regions
    associated with cancer are first tagged with
    bulky molecules. Using a nano tube tip,
    resembling the needle on a record player, the
    physical shape of the DNA can be traced. A
    computer translates this information into
    topographical map. The bulky molecules identify
    the regions on the map where mutations are
    present. Since the location of mutations can
    influence the effects they have on a cell, these
    techniques will be important in predicting
    disease.

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4.Quantum Dotes (QD)
  • These are tiny crystals that glow when these are
    stimulated by ultraviolet light. The latex beads
    filled with these crystals when stimulated by
    light, the colors they emit act as dyes that
    light up the sequence of interest. By combining
    different sized quantum dotes within a single
    bead, probes can be created that release a
    distinct spectrum of various colors and
    intensities of lights, serving as sort of
    spectral bar code.

34
5.Nanoshells (NS)
  • These are another recent invention. NS are
    miniscule beads coated with gold.
  • By manipulating the thickness of the layers
    making up the NS, the beads can be designed that
    absorb specific wavelength of light.
  • The most useful nanoshells are those that absorb
    near infrared light that can easily penetrate
    several centimeters in human tissues.
  • Absorption of light by nanoshells creates an
    intense heat that is lethal to cells. Nanoshells
    can be linked to antibodies that recognize cancer
    cells. In laboratory cultures, the heat generated
    by the light-absorbing nanoshells has
    successfully killed tumor cells while leaving
    neighboring cells intact .

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6.Dendrimer
  • A number of nanoparticles that will facilitate
    drug delivery are being developed. One such
    molecule that has potential to link treatment
    with detection and diagnostic is known as
    dendrimer.
  • These have branching shape which gives them vast
    amounts of surface area to which therapeutic
    agents or other biologically active molecules can
    be attached. A single dendrimer can carry a
    molecule that recognizes cancer cells, a
    therapeutic agent to kill those cells and a
    molecule that recognizes the signals of cell
    death.
  • It is hoped that dendrimers can be manipulated
    to release their contents only in the presence of
    certain trigger molecules associated with cancer.
    Following drug releases, the dendrimers may also
    report back whether they are successfully killing
    their targets. 
  • The technologies mentioned above are in the
    various stages of discovery and development. Some
    of the technologies like quantum dots, nano pores
    and other devices may be available for detection
    and diagnosis and for clinical use within next
    ten years.

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7.Nanoparticles
  • Nanoscale  devices  have the  potential 
    to radically  change  cancer  therapy 
    for the better  and  to dramatically  increase 
    the  number  of  highly effective  therapeutic 
    agents.
  • In  this  example, nanoparticles  are 
    targeted to  cancer  cells for  use  in the
    molecular  imaging of  a  malignant lesion. 
    Large  numbers of  nanoparticles  are 
    safely  injected  into the  body 
    and preferentially  bind  to the  cancer  cell, 
    defining  the  anatomical contour  of 
    the lesion  and  making it  visible.
  • These  nanoparticles  give us  the  ability to 
    see  cells  and  molecules  that we 
    otherwise  cannot detect  through  conventional 
    imaging.  The  ability to  pick  up  what 
    happens  in the  cell  ,  to  monitor 
    therapeutic intervention  and  to  see  when a 
    cancer  cell  is  mortally  wounded or  is 
    actually activated  ,  is critical  to  the 
    successful  diagnosis  and treatment  of 
    the disease.
  • Nanoparticulate  technology  can prove  to 
    be very  useful  in  cancer  therapy which is  
    effective  and targeted  drug  delivery  by 
    overcoming  the many  biological, 
    biophysical and  biomedical  barriers  that  the 
    body stages  against  a standard  intervention 
    such  as  the  administration  of drugs  or 
    contrast agents.

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8.Gold nanoshells
  • Here use  of  Nanoparticle  based electrochemical 
    detector  is done. 
  • Principle A  standard  glass electrode  is 
    first coated  with  chitosan, a  complex 
    sugar obtained  from  crab and  shrimp 
    shells, and  then  with  gold 
    nanoparticles.  The bold  nanoparticles 
    provide a  electrically  conductive  surface 
    upon  which cancer  cells  can stick without 
    damaging the  cells.  The  cancer  cells  can be 
    taken  from the  patient  and suspended  in  a 
    suitable  growth  solution.
  • After cells  are  allowed to  bind  to the 
    electrode,  two monoclonal  antibodies 
    are added  to  the assay  solution.  The first 
    antibody  binds  to  glycoprotein, which  the 
    second cause an electrochemical reaction  to 
    occur  only if  the  first antibody  has 
    bound to  any  glycoprotein. 
    The electrochemical  reaction  triggers an  of 
    cells  with glycoprotein  present  on  their 
    surfaces.  

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9.Nanobombs
  • the nanobomb holds great promise as a therapeutic
    agent for killing cancer cells, with particular
    emphasis on breast cancer cells, because its
    shockwave kills the cancerous cells as well as
    the biological pathways that carry instructions
    to generate additional cancerous cells and the
    small veins that nourish the diseased cells.
    Also, it can be spread over a wide area to create
    structural damage to the cancer cells that are
    close by.
  • The nanobombs are superior to a variety of
    current treatments because they are powerful,
    selective, non-invasive, nontoxic and can
    incorporate current technology, including
    microsurgery.
  • An advantage over other carbon nanotube
    treatments being considered by scientists is that
    with nanobombs, the carbon nanotubes are
    destroyed along with the cancer cells.

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Future  goals  through  Nanotechnology  in 
cancer  diagnosis  and  treatment-
  • Imaging  agents and  diagnostics  that will 
    allow  clinicians  to detect  cancer in  its 
    earliest stages. 
  • Systems  that will  provide  real time 
    assessments  of therapeutic  and  surgical 
    efficacy  for  accelerating clinical 
    translation.
  • Multifunctional  targeted devices  capable 
    of bypassing  biological  barriers  to  deliver 
    multiple therapeutic  agents  directly to 
    cancer  cells  and  those  tissues in  the 
    microenvironment  that play a critical  role 
    in  the growth  and  metastasis of cancer.
  • Agents  that can  monitor  predictive molecular 
    changes and
  • prevent  precancerous  cells from  becoming 
    malignant.
  • Novel  methods to  manage  the symptoms  of 
    cancer  that adversely  impact quality  of 
    life. 
  • Research  tools that  will  enable rapid 
    identification  of  new  targets 
    for clinical  development  and predict  drug 
    resistance. 

45
Challenges Of Technology
  • Today, much of the science on the nanoscale is
    basic research, designed to reach a better
    understanding of how matter behaves on this small
    scale.
  • The surface area of nano-materials being large,
    the phenomena like friction and sticking are more
    important than they are in large systems. These
    factors will affect the use of nanomaterials both
    inside and outside the body.
  • Nanostructures being so small the body may clear
    them too rapidly to be effective in detection or
    imaging. Larger nanoparticles may accumulate in
    vital organs, creating a toxicity problem.

46
Conclusion
  • Nanotechnology  has  made the  diagnosis 
    and treatment  of  cancer  easy,  safe, 
    and efficient.  Scientist  believe that  with 
    nanotechnology  it  would  be  possible to 
    turn  cancer   (life  threatening  disease) into 
    a  chronic and  manageable  disease.
  •  
  • Nanotechnology will radically change the way we
    diagnose, treat and prevent cancer to help meet
    the goal of eliminating suffering and death from
    cancer.
  • Although most of the technologies described are
    promising and fit well with the current methods
    of treatment, there are still safety concerns
    associated with the introduction of nanoparticles
    in the human body.

47
  • These will require further studies before some of
    the products can be approved. The most promising
    methods of drug delivery in cancer will be those
    that combine diagnostics with treatment. These
    will enable personalized management of cancer and
    provide an integrated protocol for diagnosis and
    follow up that is so important in management of
    cancer patients. There are still many advances
    needed to improve nanoparticles for treatment of
    cancers.

48
  • Future efforts will focus on identifying the
    mechanism and location of action for the vector
    and determining the general applicability of the
    vector to treat all stages of tumors in
    preclinical models. Further studies are focused
    on expanding the selection of drugs to deliver
    novel nanoparticle vectors. Hopefully, this will
    allow the development of innovative new
    strategies for cancer cures.
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