Cancer Therapy Using Nanotechnology: Dept. of Electrical Engineering, College of Engineering Trivandrum

CANCER THERAPY USING NANOTECHNOLOGY
1. INTRODUCTION
Cancer is the uncontrolled growth of abnormal cells in the body. Cancerous cells are also called malignant cells. Cells are the building blocks of living things. Cancer grows out of normal cells in the body. Normal cells multiply when the body needs them, and die when the body doesn't need them. Cancer appears to occur when the growth of cells in the body is out of control and cells divide too quickly. It can also occur when cells forget how to die. There are many causes of cancers, including:
1) 2) 3)
Benzene and other chemicals Drinking excess alcohol Environmental toxins, such as certain poisonous mushrooms and a type of poison that can grow on peanut plants (aflatoxins)
4) 5) 6) 7) 8)
Excessive sunlight exposure Genetic problems Obesity Radiation Viruses However, the cause of many cancers remains unknown. The most common
cause of cancer-related death is lung cancer. Cancer is the leading cause of death worldwide. Deaths from cancer is projected to continue rising. It is estimated to have 13.1 million deaths in 2030. Nanotechnology enables rapid and sensitive detection of cancer. It also provides therapies that aim directly and selectively at the cancerous cells. Shortcomings of the present cancer therapies such as risk damage to normal tissues and incomplete eradication of cancer are eliminated.
Dept. Of Electrical Engineering, College of Engineering Trivandrum.
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2. OBJECTIVES
1) To realize the importance to eradicate the deadly disease CANCER. 2) To understand the shortcomings of present cancer treatment. 3) To understand the importance of Nanotechnology. 4) To understand the mechanism of cancer treatment using nanotechnology. 5) To understand the present status of Nanotechnology in Cancer therapy.
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CANCER THERAPY USING NANOTECHNOLOGY 3. CANCER
Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems.
Fig 3.1 Normal Cell division and Cancer cell division Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer that begins in basal cells of the skin is called basal cell carcinoma. Cancer types can be grouped into broader categories. The main categories of cancer include:
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1)
Carcinoma - cancer that begins in the skin or in tissues that line or cover internal organs.
2)
Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.
3)
Leukemia - cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood.
4) 5)
Lymphoma and myeloma - cancers that begin in the cells of the immune system. Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord. All cancers begin in cells, the body's basic unit of life. To understand cancer, it's helpful to know what happens when normal cells become cancer cells. The body is made up of many types of cells. These cells grow and divide in a controlled way to produce more cells as they are needed to keep the body healthy. When cells become old or damaged, they die and are replaced with new cells. However, sometimes this orderly process goes wrong. The genetic material (DNA) of a cell can become damaged or changed, producing mutations that affect normal cell growth and division. When this happens, cells do not die when they should and new cells form when the body does not need them. The extra cells may form a mass of tissue called a tumor. Not all tumors are cancerous; tumors can be benign or malignant.
1)
Benign tumors aren't cancerous. They can often be removed, and, in most cases, they do not come back. Cells in benign tumors do not spread to other parts of the body.
2)
Malignant tumors are cancerous. Cells in these tumors can invade nearby tissues and spread to other parts of the body. The spread of cancer from one part of the body to another is called metastasis. Some cancers do not form tumors. For example, leukemia is a cancer of the bone marrow and blood.
Dept. Of Electrical Engineering, College of Engineering Trivandrum. Page 4

Cancer, known medically as a malignant neoplasm, is a broad group of various diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the body through the lymphatic system or bloodstream. Not all tumors are cancerous. Benign tumors do not grow uncontrollably, do not invade neighbouring tissues, and do not spread throughout the body. There are over 200 different known cancers that afflict humans . According to India cancer statistics, India has one of the highest cancer rates in the world. cancer rates in India are lower than those seen in Western countries. These India cancer statistics remind people should pay attention on their health. Cancer is a generic term for large number of diseases that affect any part of the body. Today Cancer accounts for ONE in every EIGHT deaths worldwide (more than HIV, tuberculosis and malaria combined).20000 people die due to cancer every day worldwide. Hence we can understand how important it is to develop efficient methods to tackle this deadly disease.
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4. NANOTECHNOLOGY
Nanotechnologyscience and engineering of manipulating matter at the molecular scale to create devices with novel chemical, physical and biological propertieshas the potential to radically change how we diagnose and treat cancer. Although we have only recently developed the ability to manipulate technologies on this scale, there has been great progress in moving nano-based cancer therapies into the clinic and many more are in development.
Fig 4.1 What is Nanotechnology? Nanotechnology refers to the interactions of cellular and molecular components and engineered materialstypically clusters of atoms, molecules and molecular fragmentsat the most elemental level of biology. Such nanoscale objectstypically, though not exclusively, with dimensions smaller than 100 nanometrescan be useful by themselves or as part of larger devices containing multiple nanoscale objects. Nanotechnology is being applied to almost every field
Imaginable including biosciences, electronics, magnetics, optics, information technology, and materials development, all of which have an impact on biomedicine. Nanotechnology can provide rapid and sensitive detection of cancer-related molecules, enabling scientists to detect molecular changes even when they occur only in a small percentage of cells. Nanotechnology also has the potential to generate unique and highly effective therapeutic agents. Biological processes, including events necessary for life and those that lead to cancer, occur at the nanoscale. We are, in fact, composed of biological nanomachines. Nanotechnology provides researchers with the opportunity to study and manipulate macromolecules in real time and during the earliest stages of cancer progression. Nanotechnology can provide rapid and sensitive detection of cancerrelated molecules, enabling scientists to detect molecular changes even when they occur only in a small percentage of cells. Nanotechnology also has the potential to generate entirely novel and highly effective therapeutic agents.
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5. MANUFACTURING NANO DEVICES
Nanoscale devices are one hundred to ten thousand times smaller than human cells. They are similar in size to large biological molecules ("bio molecules") such as enzymes and receptors. As an example, haemoglobin, the molecule that carries oxygen in red blood cells, is approximately 5 nanometres in diameter. Nanoscale devices smaller than 50 nanometres can easily enter most cells, while those smaller than 20 nanometres can move out of blood vessels as they circulate through the body.
Fig 5.1 Designing nano devices for use in the body Because of their small size, nanoscale devices can readily interact with biomolecules on both the surface and inside cells. By gaining access to so many areas of the
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body, they have the potential to detect disease and deliver treatment in ways unimagined before now. There are two basic approaches for creating nanodevices. Scientists refer to these methods as the top-down approach and the bottom-up approach. The top-down approach involves moulding or etching materials into smaller components. This approach has traditionally been used in making parts for computers and electronics. The bottom-up approach involves assembling structures atom-by-atom or moleculeby-molecule, and may prove useful in manufacturing devices used in medicine. The Bottom-up approaches seek to arrange smaller components into more complex assemblies. DNA nanotechnology utilizes the specificity of Watson Crick base pairing to construct well-defined structures out of DNA and other nucleic acids. The Top-down approaches seek to create smaller devices by using larger ones to direct their assembly. Many technologies that descended from conventional solid-state silicon methods for fabricating microprocessors are now capable of creating features smaller than 100 nm, falling under the definition of nanotechnology. Giant magneto resistance-based hard drives already on the market fit this description, as do atomic layer deposition (ALD) techniques. Peter Grnberg and Albert Fert received the Nobel Prize in Physics in 2007 for their discovery of Giant magneto resistance and contributions to the field of spintronics.
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6. IMPORTANCE OF NANODEVICES IN CANCER TREATMENT
Most animal cells are 10,000 to 20,000 nanometres in diameter. This means that nanoscale devices (less than 100 nanometres) 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. They may also be able to enter and monitor cells within a living body.
Fig 6.1 Nanodevices are small enough to enter the cells 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 need a new set of tools. 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.
Fig 6.2 Nanodevices can improve sensitivity Many nanotechnology tools will make it possible for clinicians to run tests without physically altering the cells or tissue they take from a patient. 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.
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Fig 6.3 Nanodevices detect cancer at a very early stage Miniaturization will allow the tools for many different tests to be situated together on the same small device. Researchers hope that nanotechnology will allow them to run many diagnostic tests simultaneously. Current imaging methods can only readily detect cancers once they have made a visible change to a tissue, by which time thousands of cells will have proliferated and perhaps metastasized. And even when visible, the nature of the tumormalignant or benignand the characteristics that might make it responsive to a particular treatment must be assessed through biopsies. Imagine instead if cancerous or even pre-cancerous cells could somehow be tagged for detection by conventional scanning devices. Two things would be necessarysomething that specifically identifies a cancerous cell and something that enables it to be seen and both can be achieved through nanotechnology. For example, antibodies that identify specific receptors found to be over expressed in cancerous cells can be coated on to nanoparticles such as metal oxides which produce a high contrast signal on Magnetic Resonance Images (MRI) or Computed Tomography (CT) scans. Once inside the body, the antibodies on these nanoparticles will bind selectively to cancerous cells, effectively lighting them up for the scanner. Similarly, gold particles could be used to enhance light scattering for endoscopic techniques like colonoscopies. Nanotechnology will enable the visualization of molecular markers

that identify specific stages and types of cancers, allowing doctors to see cells and molecules undetectable through conventional imaging.
Fig. 6.4 Preservation of samples Screening for biomarkers in tissues and fluids for diagnosis will also be enhanced and potentially revolutionized by nanotechnology. Individual cancers differ from each other and from normal cells by changes in the expression and distribution of tens to hundreds of molecules. As therapeutics advance, it may require the simultaneous detection of several biomarkers to identify a cancer for treatment selection. Nanoparticles such as quantum dots, which emit light of different colors depending on their size, could enable the simultaneous detection of multiple markers. The photoluminescence signals from antibody-coated quantum dots could be used to screen for certain types of cancer. Different colored quantum dots would be attached to antibodies for cancer biomarkers to allow oncologists to discriminate cancerous and healthy cells by the spectrum of light they see.
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Cancer therapies are currently limited to surgery, radiation, and chemotherapy. All three methods risk damage to normal tissues or incomplete eradication of the cancer. Nanotechnology offers the means to aim therapies directly and selectively at cancerous cell
Fig. 6.5 Several tests using a single device Conventional chemotherapy employs drugs that are known to kill cancer cells effectively. But these cytotoxic drugs kill healthy cells in addition to tumor cells, leading to adverse side effects such as nausea, neuropathy, hair-loss, fatigue, and compromised immune function. Nanoparticles can be used as drug carriers for chemotherapeutics to deliver medication directly to the tumor while sparing healthy tissue. Nanocarriers have several advantages over conventional chemotherapy. They can:
1) 2)
Protect drugs from being degraded in the body before they reach their target. Enhance the absorption of drugs into tumors and into the cancerous cells themselves.
3)
Allow for better control over the timing and distribution of drugs to the tissue, making it easier for oncologists to assess how well they work.
4)
Prevent drugs from interacting with normal cells, thus avoiding side effects.
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There are now several nanocarrier-based drugs on the market, which rely on passive targeting through a process known as "enhanced permeability and retention." Because of their size and surface properties, certain nanoparticles can escape through blood vessel walls into tissues. In addition, tumors tend to have leaky blood vessels and defective lymphatic drainage, causing nanoparticles to accumulate in them, thereby concentrating the attached cytotoxic drug where it's needed, protecting healthy tissue and greatly reducing adverse side effects. On the horizon are nanoparticles that will actively target drugs to cancerous cells, based on the molecules that they express on their cell surface. Molecules that bind particular cellular receptors can be attached to a nanoparticle to actively target cells expressing the receptor. Active targeting can even be used to bring drugs into the cancerous cell, by inducing the cell to absorb the nanocarrier. Active targeting can be combined with passive targeting to further reduce the interaction of carried drugs with healthy tissue. Nanotechnology-enabled active and passive targeting can also increase the efficacy of a chemotherapeutic, achieving greater tumor reduction with lower doses of the drug. Moving away from conventional chemotherapeutic agents that activate normal molecular mechanisms to induce cell death, researchers are exploring ways to physically destroy cancerous cells from within. One such technologynanoshells is being used in the laboratory to thermally destroy tumors from the inside. Nanoshells can be designed to absorb light of different frequencies, generating heat (hyperthermia). Once the cancer cells take up the nanoshells (via active targeting), scientists apply near-infrared light that is absorbed by the nanoshells, creating an intense heat inside the tumor that selectively kills tumor cells without disturbing neighbouring healthy cells. Similarly, new targeted magnetic nanoparticles are in development that will both be visible through Magnetic Resonance Imaging (MRI) and can also destroy cells by hyperthermia.
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7. CANTILEVERS
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.
Fig. 7.1 Faster and efficient testing using Cantilevers
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Nanoscale cantilevers - microscopic, flexible beams resembling a row of diving boards - are built using semiconductor lithographic techniques. These can be coated with molecules capable of binding specific substrates-DNA complementary to a specific gene sequence, for example. Such micron-sized devices, comprising many nanometre-sized cantilevers, can detect single molecules of DNA or protein. As a cancer cell secretes its molecular products, the antibodies coated on the cantilever fingers selectively bind to these secreted proteins. These antibodies have been designed to pick up one or more different, specific molecular expressions from a cancer cell. The physical properties of the cantilevers change as a result of the binding event. Researchers can read this change in real time and provide not only information about the presence and the absence but also the concentration of different molecular expressions. Nanoscale cantilevers, constructed as part of a larger diagnostic device, can provide rapid and sensitive detection of cancer-related molecules.
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8. NANOPORES
Nanopores have cancer research and treatment applications. Engineered into particles, they are holes that are so tiny that DNA molecules can pass through them one strand at a time, allowing for highly precise and efficient DNA sequencing. As a DNA strand moves through a nanopore, scientists can monitor each "letter" on it, deciphering coded information, including mutations associated with cancer. By engineering nanopores into the surface of a drug capsule that are only slightly larger than the medicine's molecular structure, drug manufacturers can also use nanopores to control the rate of a drug's diffusion in the body.
Fig 8.1 Nanopores Another interesting nanodevice is the nanopore. Improved methods of reading the genetic code will help researchers detect errors in genes that may contribute to
cancer. 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.
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9. QUANTUM DOTS
Quantum dots are miniscule semiconductor particles that can serve as signposts of certain types of cells or molecules in the body. They can do this because they emit different wavelengths of radiation depending on the type of cadmium used in their cores: cadmium sulphide for ultraviolet to blue, cadmium selenide (seen here) for most of the visible spectrum, and cadmium telluride for the far red and near-infrared. (A dot's size determines its precise colour within each range.) A polymer coating enables researchers to attach molecules such as antibodies that will seek out and attach to tumours and other targeted cells. The coating also shields nearby cells from the cadmium's toxicity. The different colours of quantum dots provide a powerful tool for labelling and monitoring multiple cells and molecules simultaneously.
Fig. 9.1 Quantum dots
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Quantum dots are tiny crystals that glow when they are stimulated by ultraviolet light. The wavelength, or colour, 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 colours 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.
Fig. 9.2 Detection of 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, cancerassociated DNA sequences visible. The diversity of quantum dots will allow scientists to create many unique labels, which can identify numerous regions of DNA simultaneously
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10. 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.
Fig. 10.1 Nanoshells 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 leaving neighbouring cells intact. They are hollow silica spheres covered with gold. Scientists can attach antibodies to their surfaces, enabling the shells to target certain cells such as cancer cells. In mouse tests, Naomi Halas's research team at Rice University directed

infrared radiation through tissue and onto the shells, causing the gold to superheat and destroy tumor cells while leaving healthy ones intact. Technicians can control the amount of heat with the thickness of the gold and the kind of laser. Nanoshells could one day also be filled with drug-containing polymers. Heating them would cause the polymers to release a controlled amount of the drug. Human trials using gold nanoshells are slated to begin in a couple of years.
Fig. 10.2 Nanoshells in Cancer therapy Gold-shelled nanoparticles, which are spherical nanoparticles with silica cores and gold shells, are used in cancer therapy and bio-imaging enhancement. Theranostic probes capable of detection and treatment of cancer in a single treatment - are nanoparticles that have binding sites on their shell that allow them to attach to a desired location (typically cancerous cells) then can be imaged through dual modality imagery (an imaging strategy that uses x-rays
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and radionuclide imaging) and through near-infrared fluorescence.. The reason gold nanoparticles are used is due to their vivid optical properties which are controlled by their size, geometry, and their surface plasmons. Gold nanoparticles (such as AuNPs) have the benefit of being biocompatible and the flexibility to have multiple different molecules, and fundamental materials, attached to their shell (almost anything that can normally be attached to gold can be attached to the gold nanoshell, which can be used in helping identifying and treating cancer). The treatment of cancer is possible only because of the scattering and absorption that occurs for plasmonics. Under scattering, the gold-plated nano-particles become visible to imaging processes that are tuned to the correct wavelength which is dependent upon the size and geometry of the particles. Under absorption, photo thermal ablation occurs, which heats the nanoparticles and their immediate surroundings to temperatures capable of killing the aids cells. This is accomplished with minimal damage to cells in the body due to the utilization of the "water window" (the spectral range between 800 and 1300 nm). As the human body is mostly water, this optimizes the light used versus the effects rendered. These gold nanoshells are shuttled into tumors by the use of phagocytosis, where phagocytes engulf the nanoshells through the cell membrane to form an internal phagosome, or macrophage. After this it is shuttled into a cell and enzymes are usually used to metabolize it and shuttle it back out of the cell. These nanoshells are not metabolized so for them to be effective they just need to be within the tumor cells and photo-induced cell death (as described above) is used to terminate the tumor cells. Nanoparticle-based therapeutics have been successfully delivered into tumors by exploiting the enhanced permeability and retention effect, a property that permits nanoscale structures to be taken up passively into tumors without the assistance of antibodies] Delivery of nanoshells into the important regions of tumors can be very difficult. This is where most nanoshells try to exploit the tumors natural recruitment of monocytes for delivery as seen in the above figure. This delivery system is called a "Trojan Horse". This process works so well since tumors are about macrophages and once monocytes are brought into the tumor, it differentiates into macrophages which would also be need to maintain the cargo nanoparticles. Once the nanoshells are at

the necrotic centre, near-infrared illumination is used to destroy the tumor associated macrophages. Additionally, these nanoparticles can be made to release antisense DNA oligonucleotides when under photo-activation. These oligonucleotides are used in conjunction with the photo-thermal ablation treatments to perform gene-therapy. This is accomplished because nanoparticle complexes are delivered inside of cells then undergo light induced release of DNA from their surface. This will allow for the internal manipulation of a cell and provide a means for monitoring a group cells return to equilibrium. Another example of nanoshell plasmonics in cancer treatment involves placing drugs inside of the nanoparticle and using it as a vehicle to deliver toxic drugs to cancerous sites only. This is accomplished by coating the outside of a nanoparticle with iron oxide (allowing for easy tracking with an MRI machine), then once the area of the tumor is coated with the drug-filled nanoparticles, the nanoparticles can be activated using resonant light waves to release the drug.
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11. NANODEVICES AS A LINK BETWEEN DETECTION, DIAGNOSIS AND TREATMENT

Researchers aim eventually to create nanodevices that do much more than deliver treatment. The goal is to create a single nanodevice that will do many things: assist in imaging inside the body, recognize precancerous or cancerous cells, release a drug that targets only those cells, and report back on the effectiveness of the treatment.
Fig. 11.1 Nanodevices as a Link between Detection,Diagnosis and Treatment
As of now different nano devices are used for each purpose like one for providing images, another one for finding pre cancerous cells and another for detecting cancerous cells, another for detecting the severity of cancer affected in such cells, another for delivering drugs for different parts in required quantities at specified locations and another one for reporting back the effectiveness of the
delivery of medicine. As formerly said research is being carried out to encapsulate all

such nano devices into one single nano device that can do all the tasks described above efficiently and hence the time required will be less for the treatment using them. Such a device is explained in the section below.
12. DENDRIMERS
Research is being done on a number of nanoparticles created to facilitate drug delivery. One such molecule with potential to link treatment with detection and diagnosis is known as a dendrimer. Dendrimers are man-made molecules about the size of an average protein, and have a branching shape. This shape gives them vast amounts of surface area to which scientists can attach therapeutic agents or other biologically active molecules. Researchers aim eventually to create nanodevices that do much more than deliver treatment.
Fig. 12.1 Dendrimers
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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. Following drug release, the dendrimers may also report back whether they are successfully killing their targets. Applications of dendrimers typically involve conjugating other chemical species to the dendrimer surface that can function as detecting agents (such as a dye molecule), affinity ligands, targeting components, radioligands, imaging
agents, or pharmaceutically active compounds In other words, one dendrimer molecule has hundreds of possible sites to couple to an active species.. Carboxylic acid and phenol terminated water soluble dendrimers were synthesized to establish their utility in drug delivery as well as conducting chemical reactions in their interiors. This might allow researchers to attach both targeting molecules and drug molecules to the same dendrimer, which could reduce negative side effects of medications on healthy cells.
Fig. 12.2 Dendrimers as Cancer Therapy Dendrimers can also be used as a solubilizing agent. Since their introduction in the mid-1980s, this novel class of dendrimer architecture has been a prime

candidate for hosts guest chemistry. Dendrimers with hydrophobic core and hydrophilic periphery have shown to exhibit micelle-like behaviour and have container properties in solution. The use of dendrimers as unimolecular micelles was proposed by Newkome in 1985. This analogy highlighted the utility of dendrimers as solubilizing agents. The majority of drugs available in pharmaceutical industry are hydrophobic in nature and this property in particular creates major formulation problems. This drawback of drugs can be ameliorated by dendrimeric scaffolding, which can be used to encapsulate as well as to solubilize the drugs because of the capability of such scaffolds to participate in extensive hydrogen bonding with water. Dendrimer labs throughout the planet are persistently trying to manipulate dendrimers solubilizing trait, in their way to explore dendrimer as drug delivery and target specific carrier. The use of dendrimers as drug carriers by encapsulating hydrophobic drugs is a potential method for delivering highly active pharmaceutical compounds that may not be in clinical use due to their limited water solubility and resulting suboptimal pharmacokinetics. Dendrimers have been widely explored for controlled delivery of antiretroviral bioactives.. The inherent antiretroviral activity of dendrimers enhances their efficacy as carriers for antiretroviral drugs. The dendrimer enhances both the uptake and retention of compounds within cancer cells, a finding that was not anticipated at the onset of studies. The encapsulation increases with dendrimer generation and this method may be useful to entrap drugs with a relatively high therapeutic dose. Studies based on this dendritic polymer also open up new avenues of research into the further development of drug-dendrimer complexes specific for a cancer and/or targeted organ system. These encouraging results provide further impetus to design, synthesize, and evaluate dendritic polymers for use in basic drug delivery studies and eventually in the clinic.
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13. WHERE IT STANDS NOW?
The application of nanotechnology to medicine includes the use of precisely engineered materials to develop novel therapies and devices that may reduce toxicity as well as enhance the efficacy and delivery of treatments. As a result, the application of nanotechnology to cancer can lead to many advances in the prevention, detection, and treatment of cancer. The first nanotechnology-based cancer drugs have passed regulatory scrutiny and are already on the market including Doxil and Abraxane. In recent years, the U.S. Food and Drug Administration (FDA) has approved numerous Investigational New Drug (IND) applications for nano-formulations, enabling clinical trials for breast, gynecological, solid tumor, lung, mesenchymal tissue, lymphoma, central nervous system and genito-urinary cancer treatments. The majority of these trials repurpose the previously approved technologies described above. Drs. Caius Radu, Owen Witte and Michael Phelps at the Nanosystems Biology Cancer Center (Caltech/UCLA CCNE) have developed a series of positron emission tomography (PET) imaging agents. These agents, known as the [ 18F]-FAC family of PET imaging agents, are being tested for use in assigning patients for chemotherapy with drugs such as gemcitabine, cytarabine, fludarabine, and others that are used to treat cancers including metastatic breast, non-small cell lung, ovarian, and pancreatic, as well as leukemia and lymphomas. Tumors that are responsive to these drugs show up as bright images in PET scans when patients are first dosed with [18F]-FAC. Biodistribution studies have been conducted in eight healthy volunteers. Clinical development is being conducted by Sofie Biosciences. Cerulean Pharma, Inc. is conducting clinical trials of a cyclodextrin-based polymer conjugated to camptothecin. This trial is also an open-label, dose-escalation study of CRLX101 (formerly named IT-101) administered in patients with solid tumor malignancies. Calando Pharmaceuticals, founded by Dr. Mark Davis at
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the Caltech/UCLA CCNE, initiated the development of and retains the rights to CRLX101. Nanotechnology is a powerful tool for combating cancer and is being put to use in other applications that may reduce pollution, energy consumption, greenhouse gas emissions, and help prevent diseases. NCI's Alliance for Nanotechnology in Cancer is working to ensure that nanotechnologies for cancer applications are developed responsibly. There is nothing inherently dangerous about being nanosized. Our ability to manipulate objects at the nanoscale has developed relatively recently, but nanoparticles are as old as the earth. Many nanoparticles occur naturally (for example, in volcanic ash and sea spray) and as by-products of human activities since the Stone Age (nanoparticles are in smoke and soot from fire). There are so many ambient incidental nanoparticles, in fact, that one of the challenges of nanoparticle exposure studies is that background incidental nanoparticles are often at order-of-magnitude higher levels than the engineered particles being evaluated. As with any new technology, the safety of nanotechnology is continuously being tested. The small size, high reactivity, and unique tensile and magnetic properties of nanomaterialsthe same properties that drive interest in their biomedical and industrial applicationshave raised concerns about implications for the environment, health, and safety (EHS). There has been some as yet unresolved debate recently about the potential toxicity of a specific type of nanomaterial carbon nanotubes (CNTs)which has been associated with tissue damage in animal studies. However, the majority of available data indicate that there is nothing uniquely toxic about nanoparticles as a class of materials. In fact, most engineered nanoparticles are far less toxic than household cleaning products, insecticides used on family pets, and over-the-counter dandruff remedies. Certainly, the nanoparticles used as drug carriers for chemotherapeutics are much less toxic than the drugs they carry and are designed to carry drugs safely to tumors without harming organs and healthy tissue.
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To insure that potential risks of nanotechnology are thoroughly evaluated, the NCI Alliance for Nanotechnology in Cancer makes the services of
its Nanotechnology Characterization Laboratory (NCL) available to the nanotech and cancer research communities. The NCL, an intramural program of the Alliance, performs nanomaterial safety and toxicity testing in vitro (in the laboratory) and using animal models. The NCL tests are designed to characterize nanomaterials that enter the bloodstream, regardless of route. This testing is just one part of the NCL's cascade of tests to evaluate the physicochemical properties, biocompatibility, and efficacy of nanomaterials intended for cancer therapy and diagnosis. To date, the NCL has evaluated more than 125 different nanoparticles intended for medical applications. The NCL works closely with the U.S. Food and Drug Administration (FDA) and National Institutes of Standards and Technology (NIST) to devise experiments that are relevant to nanomaterials, to validate these tests on a variety of nanomaterial types, and to disseminate its methods to the nanotech and cancer research communities. The NCL also facilitates the development of voluntaryconsensus standards for reliably and pro-actively measuring and monitoring environment, health and safety ramifications of nanotech applications. Whether actual or perceived, the potential health risks associated with the manufacture and use of nanomaterials must be carefully studied in order to advance our understanding of this field of science and to realize the significant benefits that nanotechnology has to offer society, such as for cancer research, diagnostics, and therapy.
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14. CONCLUSION
Nanotechnology is the development and engineering of devices so small that they are measured on a molecular scale. This emerging field involves scientists from many different disciplines, including physicists, chemists, engineers, information technologists, and material scientists, as well as biologists. Nanotechnology is being applied to almost every field imaginable, including electronics, magnetics, optics, information technology, materials development and biomedicine. Nanotechnology is the understanding and control of matter at the nanoscale, at dimensions between approximately 1 and 100 nanometres, where unique phenomena enable novel applications. Encompassing nanoscale science,
engineering, and technology, nanotechnology involves imaging, measuring, modelling, and manipulating matter at this length scale. Matter such as gases, liquids, and solids can exhibit unusual physical, chemical, and biological properties at the nanoscale, differing in important ways from the properties of bulk materials and single atoms or molecules. Some nanostructured materials are stronger or have different magnetic properties compared to other forms or sizes or the same material. Others are better at conducting heat or electricity. They may become more chemically reactive or reflect light better or change color as their size or structure is In the fight against cancer, half the battle is won based on early detection. Nanotechnology is contributing new molecular agents and methods to enable earlier and more accurate diagnosis and treatment monitoring. Cancer therapies are currently limited to surgery, radiation, and chemotherapy. All three methods risk damage to normal tissues or incomplete eradication of the cancer. Nanotechnology offers the means to aim therapies directly and selectively at cancerous cells. Nanotechnology provides researchers with the opportunity to study and manipulate macromolecules in real time and during the earliest stages of cancer progression. Nanotechnology can provide rapid and sensitive detection of cancerrelated molecules, enabling scientists to detect molecular changes even when they occur only in a small percentage of cells. Nanotechnology also has the potential to generate entirely novel and highly effective therapeutic agents.
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REFERENCES
[1] http://nano.cancer.gov-NCI Alliance for Nanotechnology in Cancer. [2] A. Jemal, R. Siegel, J. Xu, and E. Ward, Cancer statistics,2010, CA Cancer J.Clin., vol. 60,no. 5,pp. 277-300,July 2010. [3] K. Ptak, D. Farrell ,N. J. Panaro, P. Grodzinski, and A. D. Barker, The NCI Alliance for Nanotechnology in Cancer: Achievement and path forward, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol ., vol. 152,no.8,pp. 505-512,2010.
[4] Pictures courtesy: National Cancer Institute (U.S. National Institutes of Health).
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Cancer Therapy Using Nanotechnology: Dept. of Electrical Engineering, College of Engineering Trivandrum

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CANCER THERAPY USING NANOTECHNOLOGY

Dept. Of Electrical Engineering, College of Engineering Trivandrum.