Nanotechnology For Cancer Therapy

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BNCE PUSAD

NANOTECHNOLOGY FOR CANCER THERAPY Ritesh Bhusari 10/4/2005

[email protected]

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1. INTRODUCTION:Nanotechnology is the creation of useful materials, devices, and system used to manipulate matter at an incredibly small scale -- between 1 and 100 nanometers. A nanometer is one billionth of a meter - 1/80,000 the width of a human hair, or about ten times the diameter of a hydrogen atom. Such nanoscale objects can be useful by themselves, or as part of larger devices containing multiple nanoscale objects. Nanotechnology has the potential to enable the translation of molecularbased science into clinical advances, thereby facilitating major progress in the early detection, diagnosis and treatment of cancer. Nanoscale devices are the same size as many important biological objects, and therefore can be used to “see” biological activity that the naked eye cannot. They can perform tasks inside the body that would otherwise not be possible. Nanoscale devices are smaller than human cells, which are 10,000 to 20,000 nanometers in diameter, and cellular components such as mitochondria that are inside cells. Imagine curing cancer by drinking a medicine stirred into your favourite juice. A supercomputer no bigger than a human cell. A space craft no larger or more expensive than family car. These are the few promises of nanotechnology.

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2. NEED OF NANOTECHNOLOGY IN CANCER TREATMENT :There are several reasons that nanotechnology could help transform cancer research and clinical approaches to cancer care: Most biological processes, including those processes leading to cancer, occur at the nanoscale. For cancer researchers, the ability of nanoscale devices to easily access the interior of a living cell affords the opportunity for unprecedented gains on both clinical and basic research frontiers. The ability to simultaneously interact with multiple critical proteins and nucleic acids at the molecular level will provide a better understanding of the complex regulatory and signaling patterns that govern the behavior of cells in their normal state as well as the transformation into malignant cells. Nanotechnology provides a platform for integrating research in proteomics -- the study of the structure and function of proteins, including the way they work and interact with each other inside cells -- with other scientific investigations into the molecular nature of cancer.

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3. NANOTECHNOLOGY PLATFORM FOR CANCER RESEARCH :Using Broad Agency Announcements (BAAs), NCI will identify to the R&D community critical technology platform needs for cancer, such as in vivo nanotechnology imaging systems and nanotechnology-enabled systems for rapidly assessing therapeutic efficacy and addressing cancer biology processes. The program will fund 3-year technology projects through a contract mechanism that is overseen by project specialists. The project will target cancer centers, small businesses, and Federal laboratories that prepare and submit concepts and project objectives. Upon review of initial submissions, full solicitations will be sought from those of highest value. Technology programs will create platforms that are aimed at deployment for clinical application in cancer research. Applicants will be required to team with the Comprehensive Cancer Centers or SPOREs with a plan for dissemination of the technology.

4. MODES OF ITS IMPLEMENTATION :4.1 Molecular Imaging And Early Detection :Nanotechnology can have an early, paradigm-changing impact on how clinicians will detect cancer in its earliest stages. Exquisitely sensitive devices constructed of nanoscale components-such as nanocantilevers, nanowires, and nanochannels-offer the potential for detecting even the rarest molecular signals associated with malignancy. Collecting those signals for analysis could fall to nanoscale harvesters, already under development, that selectively isolate cancer-related molecules such as proteins and peptides present in minute amounts from the bloodstream or lymphatic system. Investigators have already demonstrated the feasibility of this approach using the serum protein albumin (a naturally nanoparticle), which happens to collect proteins that can signal the presence of malignant ovarian tissue. Another area with near-term potential is detecting mutations and genome instability in situ. Already, investigators have developed novel nanoscale in vitro techniques that can analyze genomic variations across different tumor types and distinguish normal from malignant cells. Nanopores are finding use as real-time DNA sequencers, and nanotubes are showing promise in detecting mutations using a scanning electron microscope. Further work could result in a nanoscale system capable of differentiating among different types of tumors accurately and quickly, information that would be invaluable to clinicians and researchers alike. Along similar lines, other investigators have developed nanoscale technologies capable of determining protein expression patterns directly from tissue using mass spectroscopy. This technique has already shown that it can identify different types of cancer and provide data that correlate with clinical prognosis.

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In addition, nanoscale devices can enable new approaches for real-time monitoring of exposures to environmental and lifestyle cancer risk factors. Such information would be important not only for identifying individuals who may be at risk for developing cancer, but also for opening the door to complex studies of gene-environment interactions as they relate to the development of or resistance to cancer.

4.2 In vivo imaging :One of the most pressing needs in clinical oncology is for imaging agents that can identify tumors that are far smaller than is possible with today's technology, at a scale of 100,000 cells rather than 1,000,000,000 cells. Achieving this level of sensitivity requires better targeting of imaging agents and generation of a bigger imaging signal, both of which nanoscale devices are capable of accomplishing. When attached to a dendrimer, for example, the MRI contrast agent gadolinium generates a 50-fold stronger signal than in its usual form, and given that nanoscale particles can host multiple gadolinium ions, affords an opportunity to create a powerful contrast agent. When linked to one of the increasing number of targeting agents, such a construct would have the potential of meeting the 100,000 cell detection level. First-generation nanoscale imaging contrast agents are already pointing the way to new methods for spotting tumors and metastatic lesions much earlier in their development, before they are even visible to the eye. In the future, implantable nanoscale biomolecular sensors may enable clinicians to more carefully monitor the disease-free status of patients who have undergone treatment or individuals susceptible to cancer because of various risk factors. Imaging agents should also be targeted to changes that occur in the environment surrounding a tumor, such as angiogenesis, that are now beyond our capability to detect in the human body. Already, various nanoparticles are being targeted to integrins expressed by growing capillaries. Given that angiogenesis occurs in distinct stages and that antiangiogenic therapies will need to be specific for a given angiogenic state, angiogenesis imaging agents that can distinguish among these stages will be invaluable to obtain optimal benefit from therapeutics that target angiogenesis.

4.3 Reporters Of Efficacy :Today, clinicians and patients must often wait months for signs that a given therapy is working. In many instances, this delay means that should the initial therapy fail, subsequent treatments may have a reduced chance of success. This lag also adversely impacts how new therapies undergo clinical testing, since it leaves regulatory agencies reluctant to allow new cancer therapies to be tested on anyone but those patients who have exhausted all other therapeutic possibilities. Unfortunately, this set of patients is far less likely to respond to any therapy, particularly to those molecularly targeted therapies that aim to stop cancer early in its progression, an approach that virtually all of our knowledge says is the best approach for treating cancer. Nanotechnology offers the potential to develop highly sensitive imaging agents and diagnostics that can determine whether a therapeutic agent is reaching its intended target

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and whether that agent is killing malignant or support cells, such as growing blood vessels. Targeted nanoscale devices may also enable surgeons to more readily detect the margins of a tumor prior to resection or to detect micro metastases in lymph nodes or tissues distant from the primary tumor, information that would inform therapeutic decisions and have a positive impact on patient quality-of-life issues. The greatest potential for immediate results in this area would focus on detecting apoptosis following cancer therapy. Such systems could be constructed using nanoparticles containing an imaging contrast agent and a targeting molecule that recognizes a biochemical signal only seen when cells undergo apoptosis. Using the molecule annexin V as the targeting ligand attached to nanoscale iron oxide particles.

5 DEVICES IT IMPLEMENT :5.1 NANOWIRE SENSOR :-

Reference: Jim Heath, California Institute of Technology In this diagram, nano sized sensing wires are laid down across a microfluidic channel. These nanowires by nature have incredible properties of selectivity and specificity. As particles flow through the microfluidic channel, the nanowire sensors pick up the molecular signatures of these particles and can immediately relay this information through a connection of electrodes to the outside world. These nanodevices are man-made constructs made with carbon, silicon and other materials that have the capability to monitor the complexity of biological phenomenon and relay the information, as it is monitored, to the medical care provider. 6

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5.2 NANOSCALE CANTILEVER :–

Reference: Jennifer West, Rice University 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 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 molecule.

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5.3 NANOSHELL :-

Reference: Jennifer West, Rice University Nanoshells have a core of silica and a metallic outer layer. These nanoshells can be injected safely, as demonstrated in animal models. Because of their size, nanoshells will preferentially concentrate in cancer lesion sites. This physical selectivity occurs through a phenomenon called enhanced permeation retention (EPR).Scientists can further decorate the nanoshells to carry molecular conjugates to the antigens that are expressed on the cancer cells themselves or in the tumor microenvironment. This second degree of specificity preferentially links the nanoshells to the tumor and not to neighboring healthy cells. As shown in this example, scientists can then externally supply energy to these cells. The specific properties associated with nanoshells allow for the absorption of this directed energy, creating an intense heat that selectively kills the tumor cells. The external energy can be mechanical, radio frequency, optical – the therapeutic action is the same.

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6. SUCCESS OF NANOTECHNOLOGY IMPLEMENTATION :The field of nanotechnology has already yielded specific products and proofs of principle demonstrated to be of value in clinical applications: Liposomes, which are first generation nanoscale devices, are being used as drug delivery vehicles in several products. For example, liposomal amphotericin B is used to treat fungal infections often associated with aggressive anticancer treatment and liposomal doxorubicin is used to treat some forms of cancer. Another recent example is work done by researchers at Massachusetts General Hospital, led by Ralph Weissleder, M.D., Ph.D., which has shown that nanoparticulate iron oxide particles can be used with magnetic resonance imaging (MRI) to accurately detect metastatic lesions in lymph nodes without surgery. In May 2004, two companies (American Pharmaceutical Partners and American BioScience) announced that the FDA accepted the filing of a New Drug Application (NDA) for a nanoparticulate formulation of the anticancer compound taxol to treat advanced stage breast cancer. Earlier-stage research has shown that nanoparticulate sensors can detect the cell death that occurs when a cancer cell succumbs to the effects of an anticancer drug. Such sensors would be of great value to clinicians, who would no longer have to wait months to determine if a cancer therapy is working before switching a patient to a course of therapy. In addition, such a sensor could greatly accelerate clinical trials of new anticancer agents, again by providing very early signals of efficacy.

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7. PROMIISE OF NANOTECHNOLGY :Nanotechnology offers a wealth of tools that are providing cancer researchers with new and innovative ways to diagnose and treat cancer. Already, nanotechnology has been used to create new and improved ways to find small tumors through imaging. Nanoscale drug delivery devices are being developed to deliver anticancer therapeutics specifically to tumors. Work is currently being done to move these new research tools into clinical practiceIn the near future, nanoscale devices could offer the potential to detect cancer at its earliest stage and simultaneously deliver anticancer agents to the discovered tumor. Indeed, nanoscale devices could be the crucial enabling technology that will turn the promise of personalized cancer therapy -where a patient receives a drug based on the exact genetic and molecular characteristics of his or her particular type of cancer -- into reality. Nanotechnology provides opportunities to prevent cancer progression. For example, nanoscale systems, because of their small dimensions, could be applied to stop progression of ductal types of breast cancers. Nanoscale cantilevers and nanowire sensors can detect biomarkers of cancer from a single cell , which heretofore was unimaginable. Nanoparticles can aid in imaging malignant lesions, so surgeons know where the cancer is, and how to remove it. Nanoshells can kill tumor cells selectively, so patients don’t suffer terrible side effects from healthy cells being destroyed. Dendrimers can sequester drugs to reduce systemic side effects, deliver multiple drugs to maximize therapeutic impact, and rapidly discern effectiveness of a drug. Biosensors can monitor genetic changes and hyperplasia to prevent cancer progression.

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8. CONCLUSION :The application discussed here is speculative. Nanotechnology ,with all it’s challenges and opportunities, is an unavoidable part of our future.The possibilities with nanotechnology are immense and numerous. The researchers are filled with optimism, and products based on this technology are beginning to make their mark. The extent to which nanotechnology will impact our lives only depend on the limits of human ingenuinity. Expanding computer and information technology capabilities for manipulating vast amounts of clinical and biological data . Advances in nanotechnology itself that make it feasible to develop devices for imaging and delivering drugs. As nanotechnology progress we may except application to become feasible at a slowly increasingly rate. Now, Nanotechnology, specifically biomedical nanotechnology, may be advancing too fast, ensuring that the technology is safe and effective. The success of efforts in the field is contingent upon scientific excellence in research and development that is both ethical and safe for the body and the environment. “It can be rightly

to be said that nanotechnology is slowly but steadily ushering in the next industrial revolution.”

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9. REFERENCES :1. “NANOTECHNOLOGY shaping the future” (page no.40) ELECTRONICS FOR YOU-AUG 04 2. http://www.nano.cancer.gov

3. http://www.videocast.nih.gov/PastEvents.asp. 4. http://www.google.com/applications+nanotechnology

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