INTRODUCTION:

The Nanomaterials are the materials which have structured components with size less than 100nm at least in one dimension. (order of a nanoparticle is 10^-9).

Nanomedicine ranges from the medical applications of nanomaterials, to nanoelectronic biosensors, and even possible future applications of molecularnanotechnology. . The size of nanomaterialsis similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications. Thus far, the integration of nanomaterials with biology has led to the development of diagnostic devices, contrast agents, analytical tools, physical therapy applications, and drug delivery vehicles.

USE OF NANOMATERIALS IN DIFFERENT MEDICINAL FIELDS:

Drug delivery:

Nanotechnology has provided the possibility of delivering drugs to specific cells using nanoparticles. The overall drug consumption and side-effects may be lowered significantly by depositing the active agent in the morbid region only and in no higher dose than needed. A targeted or personalized medicine is intended to reduce the drug consumption and treatment expenses resulting in an overall societal benefit by reducing the costs to the public health system.

Nanomedical approaches to drug delivery center on developing nanoscale particles or molecules to improve drug bioavailability. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. This can potentially be achieved by molecular targeting by nanoengineered devices. It is all about targeting the molecules and delivering drugs with cell precision. More than $65 billion are wasted each year due to poor bioavailability.

Vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. The new methods of nanoengineered materials that are being developed might be effective in treating illnesses and diseases such as cancer. This might be accomplished by self assembled biocompatible nanodevices that will detect, evaluate, treat and report to the clinical doctor automatically.

RELATED RESEARCH AND ITS IMPACT:

It is greatly observed that nanoparticles are promising tools for the advancement of drug delivery, medical imaging, and as diagnostic sensors. However, the biodistribution of these nanoparticles is still imperfect due to the complex host's reactions to nano- and microsized materials^[14] and the difficulty in targeting specific organs in the body. Nevertheless, a lot of work is still ongoing to optimize and better understand the potential and limitations of nanoparticulate systems. This is highly selective approach would reduce costs and human suffering

An example can be found in dendrimers and nanoporous materials. Another example is to use block co-polymers, which form micelles for drug encapsulation. They could hold small drug molecules transporting them to the desired location. Another vision is based on small electromechanical systems; nanoelectromechanical systems are being investigated for the active release of drugs. Some potentially important applications include cancer treatment with iron nanoparticles or gold shells. Current research in the excretory systems of mice shows the ability of gold composites to selectively target certain organs based on their size and charge. These composites are encapsulated by a dendrimer and assigned a specific charge and size. Positively-charged gold nanoparticles were found to enter the kidneys while negatively-charged gold nanoparticles remained in the liver and spleen. It is suggested that the positive surface charge of the nanoparticle decreases the rate of opsonization of nanoparticles in the liver, thus affecting the excretory pathway. Even at a relatively small size of 5 nm, though, these particles can become compartmentalized in the peripheral tissues, and will therefore accumulate in the body over time. While advancement of research proves that targeting and distribution can be augmented by nanoparticles, the dangers of nanotoxicity become an important next step in further understanding of their medical uses.

Researchers are also developing a nanoparticle to defeat viruses. The nanoparticle does not actually destroy viruses molecules, but delivers an enzyme that prevents the reproduction of viruses molecules in the patients bloodstream. Other researchers are developing nanoparticles that can delivery drugs across the brain barrier to tackle neurologic disorders. Researchers are developing a method to increase the immune response generated by vaccines by attaching the vaccine molecules to a DNA nanostructure that delivers the vaccine molecules to specific cells that are key in triggering white blood cells to an immune response.

Fig.1. Nanodrug being delivered into the artery

Protein and peptide delivery:

Protein and peptides exert multiple biological actions in human body and they have been identified as showing great promise for treatment of various diseases and disorders. These macromolecules are called biopharmaceuticals. Targeted and/or controlled delivery of these biopharmaceuticals using nanomaterials like nanoparticles and Dendrimers is an emerging field called nanobiopharmaceutics, and these products are called nanobiopharmaceuticals.

Applications and reported research studies:

Nanoparticles delivering the myelin antigens were found to induce immune tolerance in a mouse model with relapsing multiple sclerosis. Biodegradable polystyrene microparticles coated with the myelin sheath peptides reset the mouse’s immune system and prevent the disease from recurring or reduce the symptoms by halting the attack of the immune system to the protective myelin sheath coating the nerve fibers of the central nervous system. Team of researchers in Northwestern University indicated that this treatment method can potentially be used in other autoimmune diseases.

Researchers at UCLA developed a nanoparticle system with water-soluble shell encapsulated a protein derived from bird anemia virus, apoptin. Apoptin selectively sends ‘self-destruct’ signal to tumor cells and trigger the programmed cell death (apoptosis) as it builds up in the nucleus, while leaving healthy cells unharmed. In the mouse model of human breast cancer, the treatment was found to significantly reduce the tumors’ growth. This new form of treatment resembles chemotherapy and gene therapy but without the risk of harming healthy cells, a common pitfall of chemotherapy, and no probability of genetic mutation that usually accompanies gene therapy.

Cancer:

Cancer nanotechnology is an interdisciplinary area of research in science, engineering, and medicine with broad applications for molecular imaging, molecular diagnosis, and targeted therapy. The basic rationale is that nanometer-sized particles, such as semiconductor quantum dots and iron oxide nanocrystals, have optical, magnetic, or structural properties that are not available from molecules or bulk solids. When linked with tumor targeting ligands such as monoclonal antibodies, peptides, or small molecules, these nanoparticles can be used to target tumor antigens (biomarkers) as well as tumor vasculatures with high affinity and specificity. In the mesoscopic size range of 5-100 nm diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents. Recent advances have led to bioaffinity nanoparticle probes for molecular and cellular imaging, targeted nanoparticle drugs for cancer therapy, and integrated nanodevices for early cancer detection and screening. These developments raise exciting opportunities for personalized oncology in which genetic and protein biomarkers are used to diagnose and treat cancer based on the molecular profiles of individual patients

Fig.2. A schematic illustration showing how nanoparticles or other cancer drugs might be used to treat cancer

The small size of nanoparticles endows them with properties that can be very useful in oncology, particularly in imaging. Quantum dots (nanoparticles with quantum confinement properties, such as size-tunable light emission), when used in conjunction with MRI (magnetic resonance imaging), can produce exceptional images of tumor sites. These nanoparticles are much brighter than organic dyes and only need one light source for excitation. This means that the use of fluorescent quantum dots could produce a higher contrast image and at a lower cost than today's organic dyes used as contrastmedia. The downside, however, is that quantum dots are usually made of quite toxic elements.

Another nanoproperty, high surface area to volume ratio, allows many functional groups to be attached to a nanoparticle, which can seek out and bind to certain tumorcells. Additionally, the small size of nanoparticles (10 to 100 nanometers), allows them to preferentially accumulate at tumor sites (because tumors lack an effective lymphatic drainage system). A very exciting research question is how to make these imaging nanoparticles do more things for cancer. For instance, is it possible to manufacture multifunctional nanoparticles that would detect, image, and then proceed to treat a tumor? This question is under vigorous investigation; the answer to which could shape the future of cancer treatment. A promising new cancer treatment that may one day replace radiation and chemotherapy is edging closer to human trials. Kanzius RF therapy attaches microscopic nanoparticles to cancer cells and then "cooks" tumors inside the body with radio waves that heat only the nanoparticles and the adjacent (cancerous) cells.

Sensor test chips containing thousands of nanowires, able to detect proteins and other biomarkers left behind by cancer cells, could enable the detection and diagnosis of cancer in the early stages from a few drops of a patient's blood.

The basic point to use drug delivery is based upon three facts: a) efficient encapsulation of the drugs, b) successful delivery of said drugs to the targeted region of the body, and c) successful release of that drug there.

Researchers at Rice University under Prof. Jennifer West, have demonstrated the use of 120 nm diameter nanoshells coated with gold to kill cancer tumors in mice. The nanoshells can be targeted to bond to cancerous cells by conjugating antibodies or peptides to the nanoshell surface. By irradiating the area of the tumor with an infrared laser, which passes through flesh without heating it, the gold is heated sufficiently to cause death to the cancer cells.

Nanoparticles of cadmium selenide (quantum dots) glow when exposed to ultraviolet light. When injected, they seep into cancer HYPERLINK "http://en.wikipedia.org/wiki/Tumors" \o "Tumors"tumors. The surgeon can see the glowing tumor, and use it as a guide for more accurate tumor removal.

In photodynamic therapy, a particle is placed within the body and is illuminated with light from the outside. The light gets absorbed by the particle and if the particle is metal, energy from the light will heat the particle and surrounding tissue. Light may also be used to produce high energy oxygen molecules which will chemically react with and destroy most organic molecules that are next to them (like tumors). This therapy is appealing for many reasons. It does not leave a “toxic trail” of reactive molecules throughout the body (chemotherapy) because it is directed where only the light is shined and the particles exist. Photodynamic therapy has potential for a noninvasive procedure for dealing with diseases, growthand tumors.

Surgery:

At Rice University, a flesh welder is used to fuse two pieces of chicken meat into a single piece. The two pieces of chicken are placed together touching. A greenish liquid containing gold-coated nanoshells is dribbled along the seam. An infrared laser is traced along the seam, causing the two sides to weld together. This could solve the difficulties and blood leaks caused when the surgeon tries to restitch the arteries that have been cut during a kidney or heart transplant. The flesh welder could weld the artery perfectly.

Visualization:

Tracking movement can help determine how well drugs are being distributed or how substances are metabolized. It is difficult to track a small group of cells throughout the body, so scientists used to dye the cells. These dyes needed to be excited by light of a certain wavelength in order for them to light up. While different color dyes absorb different frequencies of light, there was a need for as many light sources as cells. A way around this problem is with luminescent tags. These tags are quantum dots attached to proteins that penetrate cell membranes. The dots can be random in size, can be made of bio-inert material, and they demonstrate the nanoscale property that color is size-dependent. As a result, sizes are selected so that the frequency of light used to make a group of quantum dots fluoresce is an even multiple of the frequency required to make another group incandesce. Then both groups can be lit with a single light source. They have also found a way to insert nanoparticles into the affected parts of the body so that those parts of the body will glow showing the tumor growth or shrinkage or also organ trouble.

Tissue engineering:

Nanotechnology may be able to help reproduce or repair damaged tissue. “Tissueengineering” makes use of artificially stimulated cell proliferation by using suitable nanomaterial-based scaffolds and growth factors. For example, bones could be regrown on carbon nanotubescaffolds. Tissue engineering might replace today's conventional treatments like organ transplants or artificial implants. Advanced forms of tissue engineering may lead to life extension.

Antibioticresistance:

Nanoparicles can be used in combination therapy for decreasing antibiotic resistance. It has been shown that ZincOxidenanoparticles can decrease the antibiotic resistance and enhance the antibacterial activity of Ciprofloxacin against microorganismin Vitro. Nanoparticles can interfere with the different proteins which are interacting in the antibiotic resistance or pharmacologic mechanisms of drugs.

Immune response:

Buckyballs have been investigated for the ability to "interrupt" the allergy/immune response by preventing mast cells (which cause allergic response) from releasing histamine into the blood and tissues, by binding to free radicals "dramatically better than any anti-oxidant currently available, such as vitamin E"

Arthroscope:

Nanotechnology is helping to advance the use of arthroscopes, which are pencil-sized devices that are used in surgeries with lights and cameras so surgeons can do the surgeries with smaller incisions. The smaller the incisions the faster the healing time which is better for the patients. It is also helping to find a way to make an arthroscope smaller than a strand of hair.

Diagnostic and medical devices:

Nanotechnology-on-a-chip is one more dimension oflab-on-a-chip technology. Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms. Gold nanoparticles tagged with short segments of DNA can be used for detection of genetic sequence in a sample. Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots into polymeric microbeads. Nanopore technology for analysis of nucleic acids converts strings of nucleotides directly into electronic signatures.

Nanotechnology is also opening up new opportunities in implantable delivery systems, which are often preferable to the use of injectable drugs, because the latter frequently display first-order kinetics (the blood concentration goes up rapidly, but drops exponentially over time). This rapid rise may cause difficulties with toxicity, and drug efficacy can diminish as the drug concentration falls below the targeted range.

Neuro-electronic interfaces:

Neuro-electronic interfacing is a visionary goal dealing with the construction of nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the building of a molecular structure that will permit control and detection of nerve impulses by an external computer. The computers will be able to interpret, register, and respond to signals the body gives off when it feels sensations. The demand for such structures is huge because many diseases involve the decay of the nervous system (ALS and multiple sclerosis). Also, many injuries and accidents may impair the nervous system resulting in dysfunctional systems and paraplegia. If computers could control the nervous system through neuro-electronic interface, problems that impair the system could be controlled so that effects of diseases and injuries could be overcome. Two considerations must be made when selecting the power source for such applications. They are refuelable and nonrefuelable strategies. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, magnetic, or electrical sources. A nonrefuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained.

One limitation to this innovation is the fact that electrical interference is a possibility. Electric fields, electromagnetic pulses (EMP), and stray fields from other in vivo electrical devices can all cause interference. Also, thick insulators are required to prevent electron leakage, and if high conductivity of the in vivo medium occurs there is a risk of sudden power loss and “shorting out.” Finally, thick wires are also needed to conduct substantial power levels without overheating. Little practical progress has been made even though research is happening. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system so that it is able to monitor and respond to nervous signals. The structures that will provide the interface must also be compatible with the body’s immune system so that they will remain unaffected in the body for a long time. In addition, the structures must also sense ionic currents and be able to cause currents to flow backward. While the potential for these structures is amazing, there is no timetable for when they will be available.

Medical use of nanomaterials:

Two forms of nanomedicine that have already been tested in mice and are awaiting human trials that will be using gold nanoshells to help diagnose and treat cancer, and using liposomes as vaccine adjuvants and as vehicles for drug transport. Similarly, drug detoxification is also another application for nanomedicine which has shown promising results in rats. A benefit of using nanoscale for medical technologies is that smaller devices are less invasive and can possibly be implanted inside the body, plus biochemical reaction times are much shorter. These devices are faster and more sensitive than typical drug delivery.

Statistical report of growth and development:

The graph explains the incresing demand of nanoproducts in the field of medicine.

Nanomedicine is a large industry, with nanomedicine sales reaching $6.8 billion in 2004, and with over 200 companies and 38 products worldwide, a minimum of $3.8 billion in nanotechnology R&D is being invested every year. As the nanomedicine industry continues to grow, it is expected to have a significant impact on the economy.

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Received on 28.08.2013 Accepted on 01.09.2013

Research J. Engineering and Tech. 4(4): Oct.-Dec., 2013 page 300-305