VISVESVARAYA TECHNOLOGICAL UNIVERSITY

Belgaum, Karnataka.

A Seminar Report On Nanotechnology In Cancer Therapy Submitted By Vikrant L Jadeja. 4KM08ec059

DEPARTMENT OF ELECTRONICS & COMMUNICATION ENGINEERING

KARAVALI INSTITUTE OF TECHNOLOGY (Affiliated to VTU & Approved by AICTE)

Seminar Report ON Nanotechnology In Cancer Therapy

By Vikrant L Jadeja 4KM08EC059

Guided by Ms Lavita DSouza

Department of Electronics & Communication Karavali Institute Of Technology Neerumrga-575029

DEPARTMENT OF ELECTRONICS & COMMUNICATION ENGINEERING CERTIFICATE

This is to certify that the project entitled Novel diffusion based techniques for depth estimation from defocused images has been carried out by Mr. Vikrant L Jadeja under my guidance in partial fulfillment of the degree of Bachelor of E&C Engineering of Visvesvaraya Technological University during the academic year 2011-2012. To the best of my knowledge and belief this work has not been submitted elsewhere for the award of any other degree.

Guide Ms Lavita DSouza

Examiner

Head of the Department

Abstracts
Cancer is caused by damage of genes which control the growth and division of cells. Detection/diagnose/treatment is possible by confirming the growth of the cells and treated by rectifying the damaging mechanism of the genes or by stopping the blood supply to the cells or by destroying it. Conventional detection of the cancer is done by observing the physical growth/changes in the organ by X-rays and/or CT Scans and is confirmed by biopsy through cell culture. However, the limitation of these methods is that these are not very sensitive and the detection is possible only after substantial growth of the cancerous cells. Nano Particles (NP) being of a few of nano meters size and the cells being of the size of few microns, NP can enter inside the cells and can access the DNA molecules/Genes and therefore, there is a possibility that the defect in the genes can be detected. The conventional treatment options of cancer are surgery, radiation therapy and chemo therapy. However, all the these methods have their own limitations (in surgery one loses the organ and the cancer may appear again, in radiation therapy even the healthy cells get burnt, cancerous cells burning is not uniform and the burnt part may become dead and non functional, in chemotherapy treatment is harmful to healthy cells, approach is gross and rarely successful if the cancer is in advanced stage). In the nanotechnology methods, certain NP can be designed to absorb preferentially certain wave length of radiation and if they enters in the cancerous cells, they will burn them. Nanotechnology can be used to create therapeutic agents that target specific cells and deliver toxin to kill them. The NP will circulate through the body, detect cancer associated molecular changes, assist with imaging, release a therapeutic agent and then monitor the effectiveness of the intervention. In this paper, the details of these possible detection/ diagnose/ treatment methods of nanotechnology are presented. In addition the toxic effects of NP and their regulatory aspects are also discussed.

Key word
Cancer, Nanotechnology, Cantilevers, Nanopores, Nanoshells, Quantum Dotes,Health and Environmental Effects, Nanotechnology and Toxicity, Nanotechnology and Regulatory Aspects.

Introduction: WHAT IS NANOTECHNOLOGY?

Nanotechnology refers to the interactions of cellular and molecular components and engineered materialstypically clusters of atoms, molecules, and molecular fragments--at the most elemental level of biology. Such nanoscale objects--typically, though not exclusively, with dimensions smaller than 100 nanometers--can be useful by themselves or as part of larger devices containing multiple nanoscale objects. At the nanoscale, the physical, chemical, and biological properties of materials differ fundamentally and often noninvasive access to the interior of a living cell affords the opportunity for unprecedented gains on both clinical and basic research frontiers. Unexpectedly from those of the corresponding bulk material because the quantum mechanical properties of atomic interactions are influenced by material variations on the nanometer scale. In fact, by creating nanometer-scale structures, it is possible to control fundamental characteristics of a material, including its melting point, magnetic properties, and even color, without changing the material's chemical composition. Nanoscale devices and nanoscale components of larger devices are of the same size as biological entities. They are smaller than human cells (10,000 to 20,000 nanometers in diameter) and organelles

and similar in size to large biological macromolecules such as enzymes and receptors--hemoglobin, for example, is approximately 5 nm in diameter, while the lipid bilayer surrounding cells is on the order of 6 nm thick. Nanoscale devices smaller than 50 nanometers can easily enter most cells, while those smaller than 20 nanometers can transit out of blood vessels. As a result, nanoscale devices can readily interact with bimolecular on both the cell surface and within the cell, often in ways that do not alter the behavior and biochemical properties of those molecules. From a scientific viewpoint, the actual construction and characterization of nanoscale devices may contribute to understanding carcinogenesis. The ability to simultaneously interact with multiple critical proteins and nucleic acids at the molecular scale should

provide better understanding of the complex regulatory and signaling networks that govern the behavior of cells in their normal state and as they undergo malignant transformation. Nanotechnology provides a platform for integrating efforts in proteomics with other scientific investigations into the molecular nature of cancer by giving researchers the opportunity to simultaneously measure gene and protein expression, recognize specific protein structures and structural domains, and follow protein transport among different cellular compartments. Similarly, nanoscale devices are already proving that they can deliver therapeutic agents that can act where they are likely to be most effective, that is, within the cell or even within specific organelles. Yet despite their small size, nanoscale devices can also hold tens of thousands of small molecules, such as a contrast agent or a multicomponent diagnostic system capable of assaying a cell's metabolic state, creating the opportunity for unmatched sensitivity in detecting cancer in its earliest stages. For example, current approaches may link a monoclonal antibody to a single molecule of an MRI contrast agent, requiring that many hundreds or thousands of this construct reach and bind to a targeted cancer cell in order to create a strong enough signal to be detected via MRI.

Cancer Detection
Conventional : Conventional detection of the cancer is done by observing the physical growth/changes in the organ by Xrays and/or CT Scans and is confirmed by biopsy through cell culture. However the limitation of this method is that it is not very sensitive and the detection is possible only after substantial growth of the cancerous cells. Often the treatment is also not possible once the cancer is in such an advanced stage. Nano Technology Detection : As mentioned before, nanoparticles (NP) are of a few of nm and the cells are of the size of few microns. So NP can enter inside the cells and can access the DNA molecules/Genes and, there is a possibility that the defect in the genes can be detected. DNA molecules can be detected in their incipient stage. This could be possible in vivo or in vitro. It will be shown latter that NP do show potential of cancer detection in its incipient stage. Cancer Treatment Conventional : One of the treatment option is surgery. That is, remove the cancerous part. However, the limitation is that one loses the organ and the cancer may appear again. Further, the surgery is not cancerous cell will burn it if irradiated by suitable wavelength radiation. This is kind of the analogue of radiation therapy. As mentioned before, nanotechnology can be used to create therapeutic agents that target

specific cells and deliver toxin to kill them. The NP will circulate through the body, detect cancer associated molecular changes, assist with imaging release a therapeutic agent and then monitor the effectiveness of the intervention.

DEVELOPING A CANCER NANOTECHNOLOGY PLAN:

This latter facility will develop important standards for nanotechnological constructs and devices that will enable researchers to develop cross-functional platforms that will serve multiple purposes. The laboratory will be a centralized characterization laboratory capable of generating technical data that will assist researchers in choosing which of the many promising nanoscale devices they might want to use for a particular clinical or research application. The six major challenge areas of emphasis include:

Prevention and Control of Cancer

Developing nanoscale devices that can deliver cancer prevention agents Designing multicomponent anticancer vaccines using nanoscale delivery vehicles

Early Detection and Proteomics

Creating implantable, biofouling-indifferent molecular sensors that can detect cancer-associated biomarkers that can be collected for ex vivo analysis or analyzed in situ, with the results being transmitted via wireless technology to the physician. Developing "smart" collection platforms for simultaneous mass spectroscopic analysis of multiple cancer-associated markers.

Imaging Diagnostics
Designing "smart" injectable, targeted contrast agents that improve the resolution of cancer to the single cell level engineering nanoscale devices capable of addressing the biological and evolutionary diversity of the multiple cancer cells that make up a tumor within an individual.

Multifunctional Therapeutics
Developing nanoscale devices that integrate diagnostic and therapeutic functions creating "smart" therapeutic devices that can control the spatial and temporal release of therapeutic agents while monitoring the effectiveness of these agents

Quality of Life Enhancement in Cancer Care

Designing nanoscale devices that can optimally deliver medications for treating conditions that may arise over time with chronic anticancer therapy, including pain, nausea, loss of appetite, depression, and difficulty breathing.

Interdisciplinary Training
Coordinating efforts to provide cross-training in molecular and systems biology to nanotechnology engineers and in nanotechnology to cancer researchers. Creating new interdisciplinary coursework/degree programs to train a new generation of researchers skilled in both cancer biology and nanotechnology.

NANOTECHNOLOGY AND DIAGNOSTICS:

TOday, cancer-related nanotechnology research is proceeding on two main fronts: laboratorybased diagnostics and in vivo diagnostics and therapeutics. Nanoscale devices designed for laboratory use rely on many of the methods developed to construct computer chips. For example, 12 nanometer-wide wires built on a micron-scale silicon grid can be coated with monoclonal antibodies directed Cancer cell against various tumor markers. With minimal sample preparation, substrate binding to even a small number of antibodies produces a measurable change in the device's conductivity, leading to a 100-fold increase in sensitivity over current diagnostic techniques.

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 nanometer-sized cantilevers, can detect single molecules of or protein. Researchers have also been developing wide variety of nanoscale particles to serve as diagnostic platform devices. For example; DNA-labeled magnetic nanobeads have the potential to serve as a versatile foundation for detecting virtually any protein or nucleic acid with far more sensitivity than is possible with conventional methods now in use. If this proves to be a general property of such systems, nanoparticle-based diagnostics could provide the means of turning even the rarest a DNA

biomarkers into useful diagnostic or prognostic indicators. Quantum dots, nanoscale crystals of a semiconductor material such as cadmium selenide, are another promising nanoscale tool for laboratory diagnostics. A product of the quest to develop new methods for harvesting solar energy, these coated nanoscale semiconductor crystals act as molecular light sources whose color depends solely on particle size. When linked to an antibody or other molecule capable of binding to a substance of interest, quantum dots act like a beacon that lights up when binding occurs. Because of the multitude of colors with which they can emit light, quantum dots can be combined to create assays capable of detecting multiple substances simultaneously. In one demonstration, researchers were able to simultaneously measure levels of the breast cancer marker Her-2, actin, microfibril proteins, and nuclear antigens.

NANOTECHNOLOGY AND CANCER THERAPY:

Nanoscale devices have the potential to radically change cancer therapy for the better and to dramatically increase the number of highly effective therapeutic agents. Nanoscale constructs, for

example, 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. Already, research has shown that nanoscale delivery devices, such as dendrimers (spherical, silica-coated nanoparticles, branched micelles, and polymers), ceramic cross-linked

liposomes, can be targeted to cancer cells. This is done by attaching monoclonal antibodies or cellsurface receptor ligands that bind specifically to molecules found on the folate surfaces receptor of and cancer luteinizing cells, such as the high-affinity hormone releasing hormone (LHRH), or molecules unique to endothelial cells that become co-opted by malignant cells, such as the integrin Once they reach their target, the nanoparticles are rapidly taken into cells. As efforts in proteomics and genomics uncover other molecules unique to cancer cells, targeted nanoparticles could become the method of choice for delivering anticancer drugs directly to tumor cells and their supporting endothelial cells. Eventually, it should be possible to mix and match anticancer drugs with any one of a number of nanotechnology-based delivery vehicles and targeting agents, giving researchers the opportunity to finetune therapeutic properties without needing to discover new bioactive molecules. On an equally unconventional front, efforts are focused on constructing robust "smart" nanostructures that will eventually be capable of detecting malignant cells in vivo, pinpointing their location in the body, killing the cells, and reporting back that their payload has done its job. The operative principles driving these current efforts are modularity and multifunctional, i.e., creating functional building blocks that can be snapped together and modified to meet the particular demands of a given clinical situation. A good example from the biological world is a virus capsule, made from a limited set of proteins, each with a specific chemical functionality, that comes together to create a multifunctional nanodelivery vehicle for genetic material. In fact, at least one research group is using the empty RNA virus

capsules from cowpea mosaic virus and flockhouse virus as potential nanodevices. The premise is that 60 copies of coat protein that assemble into a functional virus capsule offer a wide range of chemical functionality that could be put to use to attach homing molecules--such as monoclonal antibodies or cancer cell-specific receptor antagonists, and reporter molecules--such as magnetic resonance imaging (MRI) contrast agents, to the capsule surface, and to load therapeutic agents inside the capsule. While such work with naturally existing nanostructures is promising, chemists and engineers have already made substantial progress turning synthetic materials into multifunctional nanodevices. Dendrimers, 1- to 10-nanometer spherical polymers of uniform molecular weight made from branched monomers, are proving particularly adept at providing multifunctional modularity. In one elegant demonstration, investigators attached folate--which targets the high-affinity folate receptor found on some malignant cells, the indicator fluoresce in, and either of the anticancer drugs methotrexate or paclitaxel to a single dendrimer. Both in vitro and in vivo experiments showed that this nanodevice delivered its therapeutic payload specifically to folate receptor-positive cells while simultaneously labeling these cells for fluorescent detection. Subsequent work, in which a fluorescent indicator of cell death was, linked to the dendrimer, provided evidence that the therapeutic compound was not only delivered to its target cell but also produced the desired effect. Already, some dendrimer-based constructs are making their way toward clinical trials for treating a variety of cancers. Such multifunctional nanodevices, sometimes referred to as nanoclinics, may also enable new types of

Therapeutic approaches or broader application of existing approaches to killing malignant cells. For example, silica-coated lipid micelles containing LH-RH as a targeting agent have been used to deliver iron

oxide particles to LH-RH receptor- positive cancer cells. Once these so-called nanoclinics have been taken up by the target cell, they can not only be imaged using MRI, but can also be turned into molecular-scale thermal scalpels: applying a rapidly oscillating magnetic field causes the entrapped molecules to

become hot enough to kill the cell. The critical factor operating here is that nanoparticles can entrap 10,000 or more molecules, providing both enhanced sensitivity for detection and enough thermal

mass to destroy the cell. Photosensitizes used in photodynamic therapy, in which light is used to generate reactive oxygen locally within tumors, have also been entrapped in targeted nanodevices. The next step in this work is to also entrap a light-generating system, such as the luciferin-luciferase pair, in such a way as to trigger light production only after the nanoparticles have been taken up by a targeted cell. If successful, such an approach would greatly extend the usefulness of photodynamic therapy to include treatment of tumors deep within the body. Such multifunctional nanodevices hold out the possibility of radically changing the practice of oncology, perhaps providing the means to survey the body for the first signs of cancer and deliver effective therapeutics during the earliest stages of the disease. Certainly, researchers envision a day when a smart nanodevice will be able to fingerprint a particular cancer and dispense the correct drug at the proper time in a malignant cell's life cycle, making individualized medicine a reality at the cellular level.

With the focus on modularity and multifunctionality, one goal is to create and characterize platform technologies that can be mixed and matched with new targeting agents that will come from large-

scale proteomics programs already in action and therapeutics both old and new. Accomplishing this goal, however, will require that engineers and biologists work hand in hand to combine the best of both of their worlds in the fight against cancer.

A POWERFUL RESEARCH ENABLER

Nanotechnology is providing a critical bridge between the physical sciences and engineering, on the one hand, and modern molecular biology on the other. Materials scientists, for example, are learning the principles of the nanoscale world by studying the behavior of bimolecular and bimolecular assemblies. In return, engineers are creating a host of nanoscale tools that are required to develop the systems biology models of malignancy needed to better diagnose, treat, and ultimately prevent cancer. In particular, biomedical nanotechnology is benefiting from the combined efforts of scientists from a wide range of disciplines, in both the physical and biological sciences, who together are producing many different types and sizes of nanoscale devices, each with its own useful characteristics.

NATIONAL RESEARCH

NANOTECHNOLOGY

STANDARDIZATION

LABORATORY

FOR

CANCER

As part of its cancer nanotechnology program, the National Cancer Institute is establishing a national resource laboratory at its Frederick facility that will provide critical infrastructure support to this rapidly developing field. The National Nanotechnology Standardization Laboratory (NSL) will fill a major resource gap in biomedical nanotechnology by providing nanodevice assessment and standardization capabilities that many experts have identified as a critical requirement to rapidly integrating nanotechnology into the clinical realm. The basic functions carried out by the NSL will include: nanoscale GMP synthesis of sizable quantities of a variety of nanoparticles and nanodevices. Characterization of nanoparticles and devices. Functionalization of nanoparticles. Development of tools and methods for characterizing both native and functionalized nanoparticles. Creation of reference standards and release specifications and Facilitation of testing and analysis protocol development that will speed the regulatory review of novel diagnostics, therapeutics, and prevention strategies that use devices.

Conclusion:
Cancer Nanotechnology is a disruptive technologywhich will drive a new generation of cancer diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes and reduce the problem of cancer dramatically in the future by this development of nanotechnology where we are going to have Nanotechnology-based sensors for genetic and protein-based monitoringHigh sensitivity and specificityLabel-free detectionDNA and protein detection on the same platform. Simultaneously Nanotech Will Enable Early Detection of Cancer and improves it.

References:
1. Understanding nano devices National nano technology initiative2. http://www.nano.gov/