REVOLUTION IN TREATMENT OF CANCER

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REVOLUTION IN TREATMENT OF CANCER

• BY
• NANOTECHNOLOGY

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• 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.

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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.

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• 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.

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Core features of cancer cells-

• Abnormal growth control
• Improved cell survival
• Abnormal differentiation
• Unlimited replicated potential
• Host tumor symbiosis

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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.

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• 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.

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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.

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• 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.

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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.

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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.

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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 .

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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 .

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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

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Transmembrane drug delivery to intracellular
targets

• Cytoporter
• Receptor-mediated endocytosis
• Transduction of proteins and Peptides
• Vitamins as carriers for anticancer agents

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Biological Therapies

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

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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.

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• 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.

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• 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.

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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. 

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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

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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.

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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. 

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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.

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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.

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• 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.

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• 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.