www.asiabiotech.com Special Feature - Nanobiotechnology/Nanomedicine

Applications of Nanomedicine by Sanjeeb K Sahoo, Ph.D

Introduction

ne of the most promising applications of nanotechnology is in the fi eld of medicine. Indeed, a whole new fi eld of “nanomedicine” is emerging. Nanomedicine has been defi ned as the monitoring, repair, Oconstruction and control of human biological systems at the molecular level using engineered nanodevices and nanostructures.1 It can also be regarded as another implementation of nanotechnology in the fi eld of medical science and diagnostics. The National Cancer Institute and the National Aeronautics & Space Administration, USA are working to develop nano-sized technologies that can detect, diagnose, and treat disease. Researchers in this fi eld are “confi dent that they are going to turn healthcare inside out.” Richard Smalley, a Nobel Prize-winning chemist at Rice University, USA, described to the Congress how the potential of nanotechnology can transform medicine: Twenty years from now, nanotechnology will have given us specially engineered drugs that specifi cally target just the mutant cancer cells in the human body, and leave everything else blissfully alone. Cancer will be a thing of the past.2 Nanotechnology can be defi ned as the science and engineering involved in the design, synthesis, characterization, and application of materials and devices whose smallest functional organization in at least one dimension is on the nanometer scale or one billionth of a meter. The prefi x “nano” is derived from the Greek word for dwarf. One nanometer (nm) is equal to one-billionth of a meter, or about the width of six carbon atoms or ten water molecules. A human hair is approximately 80,000 nm wide, and a red blood cell approximately 7000 nm wide. Atoms are below a nanometer in size, whereas many molecules, including some proteins, range from a nanometer upwards. Current applications of nanotechnology in medicine range from research involving diagnostic devices and drug delivery vehicles to robots that can enter the body and perform specifi c tasks. In the near future, applications of nanomedicine will involve engineered molecules to develop drugs, drug delivery techniques, diagnostics, medical devices and enhanced gene therapy and tissue engineering procedures.3

Nanomedicine as a Potential Platform for Therapeutic Applications

Applications of nanotechnologies in medicine are especially promising, and areas such as disease diagnosis, drug delivery targeted at specifi c sites in the body and molecular imaging are being intensively investigated and some products are undergoing clinical trials. Nanotechnology is relatively new. Although the full scope of contributions these technological advances will make in medicine is unexplored, recent advances suggested nanotechnology will have a profound impact on disease prevention, diagnosis, and treatment. The current generation of drugs is largely based on small molecules with a mass of 1000 Da or less that circulate systemically. Common deleterious consequences of systemic biodistribution include toxicity to nontarget tissues, diffi culty in maintaining drug concentrations within therapeutic windows, and metabolism and excretion of drugs, all of which can reduce effi cacy. Drug solubility and cell permeability issues are also common with small molecules and biologics. Nanotechnology-based delivery systems could mitigate these problems by combining tissue- or organ-specifi c targeting with therapeutic action. Multifunctional nano-delivery systems could also combine targeting, diagnostic, and therapeutic actions. More than 90 years ago, Nobel laureate German immunologist Paul Ehrlich proposed the so-called magic bullets artifi cial biochemical agents that would transport and release drugs at only desired

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sites in the body. Targeting the delivery of drugs to diseased lesions is one of the important aspects of the drug delivery systems. To convey a suffi cient dose of drug to the lesion, suitable carriers of drugs are needed. Although opportunities to develop nanotechnology-based effi cient drug delivery systems extend into all therapeutic classes of pharmaceuticals, the development of effective treatment modalities for the respiratory, central nervous system, and cardiovascular disorders remains a fi nancially and therapeutically signifi cant need. Many therapeutic agents have not been successful because of their limited ability to reach to the target tissue. In addition, faster growth opportunities are expected in developing delivery systems for anti-cancer agents, hormones, and vaccines owing to safety and effi cacy shortcomings in their conventional administration modalities. For example, in cancer chemotherapy, cytostatic drugs damage both malignant and normal cells alike. Thus, a drug delivery strategy that selectively targets the malignant tumor is very much needed. Additional problems include drug instability in the biological milieu and premature drug loss through rapid clearance and metabolism. Similarly, high protein binding of certain drugs such as protease inhibitors limits their diffusion to the brain and other organs. However, nanotechnology for drug delivery applications may not be suitable for all drugs, especially those drugs that are less potent because the higher dose of the drug would make the drug delivery system more massive, which would be diffi cult to administer. Drug bioavailability is a related problem with potential nanotechnology solutions. Nanotechnology is opening up new therapeutic opportunities for a large number of agents that cannot be used effectively as conventional oral formulations, due to poor bioavailability. In some cases, reformulation of a drug with smaller particle size may improve oral bioavailability. Nanoparticles formulations provide protection for agents susceptible to degradation or denaturation in regions of harsh pH, and also prolong the duration of exposure of a drug by increasing retention of the formulation through bioadhesion. Another broad application of nanotechnology is the delivery of antigens for vaccination. Mucosal immunity is extremely important in disease prevention, but continues to be limited by both degradation of the vaccine and limited uptake. Recent advances in encapsulation and development of suitable animal models have demonstrated that micro and nanoparticles are capable of enhancing immunization. It has been shown that M cells in the Peyer’s Patches of the distal small intestine are capable of engulfi ng large microparticles and recent studies have explored the benefi ts of nanoencapsulation.

Nanomedicine as Diagnostic Purposes

Biomedical laboratory diagnosis plays a key role in today’s health care. Most testing is done on a macroscopic scale, for example, in micro titer plates. Size reduction of biomedical lab tests has several advantages: Not only does it lead to a marked reduction of the sample volume needed for testing, but it also results in a marked reduction of (potentially expensive) reagents such as monoclonal antibodies. Last but not least, it may lead to a signifi cant reduction in the time required. Moreover, the ability of current nanotools to measure interaction microforces between individual molecules is most promising for biomedical testing because this might eliminate the need for reagent labeling, a tedious and expensive step. Taken together, small sized sample volumes and fast reaction times bring mobile testing devices into the realm of reality. They indicate that there will be a strong trend toward point-of-care testing at the bedside or in an ambulatory setting. One of the fi rst applications of nanomedicine will be improved fl uorescent markers for diagnostic and screening purposes. Conventional fl uorescent markers require complex color. Non invasive imaging techniques had a major impact in medicine over the past 25 years or so. The current drive in developing techniques such as functional magnetic resonance imaging (MRI) is to enhance spatial resolution and contrast agents. Nanotechnologies already offer the possibility of intracellular imaging through attachment of quantum dots or synthetic chromophores to selected molecules, for example, proteins, or by the incorporation of naturally occurring fl uorescent proteins which, with optical techniques such as confocal microscopy and

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correlation imaging, allows intracellular biochemical processes to be investigated directly. One application is improved imaging of the human (or any) body. Before you can treat a disease, you must diagnose it. Advances in nanotechnology have led to the design and construction of structures at the nanometer scale, in a precisely controlled manner. Amongst these improved nanostructures, nanoprobes (particles <100 nm) have stimulated a strong interest in the area of biological and clinical research. Unlike macroscale structures, nanoscale structures have optical and electronic properties that can be tuned by the structure’s size, shape or material composition. These properties offer engineers, clinicians, and researchers an unlimited supply of precursor materials for the design of contrast agents for imaging applications, optical switches for triggering drug release, or for therapy Nanotechnology could signifi cantly improve diagnostic capabilities. Nanomedicine will increase the effi ciency and accuracy of diagnosis from samples of body fl uids. For example, some companies are attempting to develop microchips that use electrodes to identify the dielectric properties of cancerous cells, viruses, and bacteria in body fl uids. Nanomedicine could result in non invasive devices that can enter the body to determine glucose levels, distinguish between normal and cancerous tissues, and provide genetic screening for multiple diseases. For example, researchers are working with a nanoscale needle that can probe cells for carcinogenic chemicals. Ultimately, research in this area could yield a tiny pill that will travel through the body and provide a comprehensive diagnosis of the patient’s health. There are even some who suggest that tiny devices could be implanted to constantly monitor health. As one reporter speculated, a person in the future may look at her watch, and it will read: “Slow down, your pulse is too high, and you are about to have a heart attack.”

Conclusion

The genesis of nanomedicine can be traced to the promise of revolutionary advances across medicine, communications and human health care. The health care revolution brought about by nanomedicine could dwarf all other trends in the history of medical technology. Although the FDA should be relatively prepared for some of the earliest and most basic applications of nanomedicine in areas such as gene therapy and tissue engineering, more advanced applications of nanomedicine will pose unique challenges in terms of classifi cation and maintainence of scientifi c expertise. The agency should begin to prepare now for the coming revolution in nanomedicine.

Contact Details: References Name: Sanjeeb K Sahoo, Ph.D. 1. Robert Freitas, Nanomedicine 2, 1999, available at Address: Laboratory for Nanomedicine, http://www.foresight.org / Nanomedicine Institute of Life Sciences, 2. Robert Freitas, supra note 29, at 26 (quoting Smalley Nalco Square, Chandrasekharpur, in testimony before a congressional sub committee about the promise of nanotechnology). Bhubaneswar, Orissa, India 3. Rocco MC, Nanotechnology: convergence with Tel: +91 674 2300137 modern biology and medicine. Curr Opin Fax: +91 674 2300728 Biotechnol. (2003) 3, 337-46. Email: [email protected]

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