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NANOTECHNOLOGY IN CANCER CHEMOTHERAPY

S.M.Arif Babjan S. Manasa B. Muralikrishna

Srinivasa Institute of Pharmaceutical Sciences Proddatur

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. Nanoscale devices are one hundred to ten thousand times smaller than human cells. They are similar in size to large biological molecules ("biomolecules") such as enzymes and receptors. As an example, hemoglobin, the molecule that carries oxygen in red blood cells, is

approximately 5 nanometers in diameter. Nanoscale devices smaller than 50 nanometers can easily enter most cells,

while those smaller than 20nanometers can move out of blood vessels as they circulate through 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 body, they have the potential to detect disease and deliver treatment in ways unimagined before now. Nanowires can detect the presence of altered genes associated with cancer. Cantilevers

microscopic, flexible beamscan provide rapid and sensitive detection of cancer-related molecules. Nanoshells can

selectively link to cancer cells, delivering therapeutic treatment directly to kill tumor cells and not harm neighboring healthy cells. Cancer therapies are currently limited to surgery, radiation, and chemotherapy. All three methods risk damage to normal tissues or incomplete eradication of the cancer.

Nanowires:

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.

They can detect the presence of altered genes associated with cancer and may help researchers pinpoint the exact lo Nanoshells

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.

The result is greater efficacy of the therapeutic treatment and a significantly reduced set of side effects. cation of those changes.

Nanotechnology offers the means to aim therapies directly and selectively at cancerous cells. One treatment involves targeted chemotherapy that delivers a tumor-killing agent called tumor necrosis factor alpha (TNF) to

cancer tumors. TNF is attached to a gold nanoparticle along with Thiol-derivatized polyethylene glycol (PEG-THIOL), which hides the TNF bearing nanoparticle from the immune system. This allows the nanoparticle to flow through the blood stream without being attacked. The combination of a gold

nanoparticle, TNF and PEG-THIOL is named Aurmine. The nanoparticle carrying the TNF tends to accumulate in cancer tumors but does not appear to accumulate in other regions of the body, which limits the toxic effects of TNF on healthy cells. CytImmune uses a combination of two techniques to target the TNF-carrying nanoparticle to cancer tumors. First, the

nanoparticle is designed to be too big to exit most healthy blood vessels, however some blood vessels located at the site of tumors are leaky, allowing the nanoparticle to exit the blood vessel at the tumor site. The second technique involves the TNF molecules binding to the tumor. The fact that they had to get all these details right, determine the right size, a way to hide the nanoparticle from the immune system as well as choosing a targeting molecule to bind to the

cancer tumor, gives you some idea as to why it has taken a while to go from research concept to clinical testing. Many researchers attach ethylene glycol

molecules to nanoparticles that deliver therapeutic drugs to cancer tumors. The ethylene glycol molecules stop white blood cells from recognizing the nanoparticles as foreign materials, allowing them to circulate in the blood stream long enough to attach to cancer tumors. However researchers at the University of California, San Diego believe that they can increase the time nanoparticles can circulate in the blood stream. They are coating nanoparticles containing therapeutic drugs with

membranes from red blood cells and have shown that these nanoparticles will circulate in a mouse's blood stream for almost two days, instead of the few hours observed for nanoparticles using ethylene glycol molecules.

Researchers are also continuing to look for more effective methods to target nanoparticles carrying therapeutic drugs directly to diseased cells. For example scientists are MIT have

demonstrated increased levels of drugs delivery to tumors by using two types of nanoparticles. The first type of nanoparticle locates the cancer tumor and the second type of nanoparticle (carrying the therapeutic drugs) homes in on a signal generated by the first type of nanoparticle.

TNF has been shown to be most effective when administered with other chemotherapy drugs.Therefore, now that the phase 1 trial involving 16 patients is over, CytImmune is planning a phase 2 trial with Aurmine combined with other chemotherapy drugs. They are also performing pre-clinical testing of another combination in which TNF, PEG-THIOL and a chemotherapy drug called paclitaxel is bound to the surface of the nanoparticle. Three other treatments are under development using nanoparticles combined with TNF and other

chemotherapy drugs. It will take a while to bring these treatments through all the phases required for qualification with the FDA, however it is exciting that they have progressed

from the realm of research papers to trials that will lead to targeted treatment for patients. Another technique delivers chemotherapy

drugs to cancer cells and also applies heat to the cell. Researchers are using gold nanorods to which DNA strands are attached. The DNA strands act as a scaffold, holding together the nanorod and the chemotherapy drug. When Infrared light illuminates the cancer tumor the gold nanorod absorbs the infrared light, turning it into heat. The heat both releases the chemotherapy drug and helps destroy the cancer cells.

The NCI Alliance for Nanotechnology in Cancer has put the tools and resources in place to help investigators explore and capitalize on opportunities to collaborate with researchers across the Alliance and beyond. This collaboration has already led to the rapid development of novel and innovative nanoscale technologies that are providing meaningful advances in cancer detection, diagnosis, and treatment.

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.

References : NCI nanotechnology-U.S www.understandingnano.com www.cancer.gov Source : INTERNET Corresponding author email :
arif.shaik88@gmail.com

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