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Written by: Simon Tse
Written on: November 1st, 2005
Tags: biomedical engineering, health & medicine
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About the Author
During the Fall 2005 semester, Simon was an engineering student at the University of Southern California.
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Volume VIII Issue I > Applying Nanotechnology to the Battle Against Cancer
Nanotechnology is a developing field in engineering. The possibilities of nanotechnology currently seem endless with all of the things that can be solved on the nano scale. With that in mind, one of the currently most promising areas of research in the field is in the discipline of Biomedical Engineering. Focusing in on cancer treatments, research has shown that nanotechnology has the ability to develop cancer treatments that are more effective and have few to no side effects. These therapeutics would bring the fight against cancer to a new level and have the potential to change the way people view the fight against cancer.

Introduction

Imagine taking a standard size 12 point font period, dividing it into roughly 150,000 equally sized pieces, and manufacturing a device averaging the size of just one of these pint size pieces. Considering the potential use of such devices, nanotechnology research, especially within the medical field, is gaining momentum. In fact, an estimated $180 billion will be allotted to nanotechnology medical research by the year 2015 [1]. An important branch of this medical exploration lies in cancer diagnosis and treatment, and researchers are already on the brink of developing several nano-scale devices designed to detect and potentially battle different forms of cancer.

Cancer Formation

According to the American Cancer Society (ACS), approximately 1,373,910 individuals were diagnosed with cancer in 2005 while another 570,280 people died from the disease [2]. In fact, statistics indicate that approximately 40% of all individuals will develop some form of cancer within their lifetime [3], a startling fact considering the lack of a cure or even a comprehensive understanding of the disease. This risk, however, must be taken with the understanding that the use of or exposure to certain substances, including cigarettes and alcohol, can dramatically increase the likelihood of cancer formation; individuals living a healthy lifestyle can cut their chance of disease development in half [3].
Initially, decades of research concluded that the introduction of mutagens could be ascribed as the single cause of cancer. Mutagens invade a cell and attack a critical gene dubbed the "proto-oncogene", which is essentially a dormant version of cancer-causing genes [3]. When introduced to mutagenic chemicals, proto-oncogenes become activated, transforming into cancer-causing oncogenes. Cells containing oncogenes multiply uncontrollably and pass the oncogene on to daughter cells, thus creating a growing number of cancer cells [3]. A collection of the cancer cells constitutes a tumor.
However, more recent studies seem to disprove those initial conclusions. It appears that multiple processes, a series of critical mutations, are required for a cell's transformation into a cancer cell. These critical mutations primarily involve the deactivation of tumor suppression genes and the activation of oncogenes [3]. As the name indicates, a tumor suppression gene is a cell's line of defense against turning into a cancer cell. With the deactivation of the suppression gene, the oncogene will encourage rapid cell division and exponentially increase the probability of tumor development [3]. The mutated cell must now sustain itself within the body and continue to rapidly multiply before a tumor can officially develop.
Activation of the oncogene does not necessarily mean that an individual will develop cancer. The body provides multiple lines of defense against cancer formation. For example, certain white blood cells known as "natural killer" (NK) cells recognize and destroy the body's own mutated cells [3]. There are also certain enzymes in the body, such as N-acetyl transferases (NAT), which protect against natural mutagens. Such enzymes are also found in foods like celery and bean sprouts [3]. Unfortunately, some mutated cells are able to evade the body's natural defense mechanisms, generally leading to tumor formation. A nascent tumor must remain relatively small in order to receive sufficient nourishment and oxygen to survive [3]. As the tumor enlarges, it actually will develop its own peripheral circulation to provide essential nutrients [3].
Once self-sufficient, the tumor can further wreak havoc on the body by releasing cancerous cells thorough the body in a process known as metastasis. The mutated cells venture to other portions of the body through the circulation system, often creating secondary tumors. This is especially dangerous as an estimated 90% of cancer deaths are related to secondary tumors, whereas only 10% of deaths are due to the initial tumors [3. For example, prostate cancer migrates to the bones and breast cancer travels to the lungs [4].

Current Cancer Treatments

A better understanding of the causes of cancer has helped doctors develop several methods to fight the disease. Such treatments include surgery, radiotherapy, and chemotherapy. Surgery is used to remove relatively large tumors. However, surgery does not eliminate all cancer cells. The remaining cancer cells may cause recurring tumors. Therefore, surgery must be supplemented with other forms of treatment.
Radiotherapy can be used as a supplement to surgery to fight cancer. Radiotherapy uses a special kind of energy, ionizing energy, which is applied over a certain area that contains the tumor [5]. The ionizing energy damages the nuclear genetic material of the cancer cell, thereby preventing it from properly multiplying. Although sound in theory, radiotherapy can only work on the targeted area, meaning that if there are mutated cells outside the target area, they will not be eradicated by the treatment. This often means multiple treatments, along with the numerous side effects that accompany radiotherapy.
The most widely known form of cancer treatment is chemotherapy. Chemotherapy battles cancer by killing all cells experiencing high rates of cellular division, which includes cancer cells and some healthy cells from the bone marrow, GI Tract, and hair follicles [6]. The benefit of chemotherapy over radiotherapy is that chemotherapy works throughout the body, thus eliminating the initial and any secondary tumor sites. Chemotherapy is given in four different manners: intravenously, orally, topically, and through injection [6]. However, use of chemotherapy for the complete eradication of cancerous cells often falls short. Like radiotherapy, chemotherapy patients require multiple treatments to eliminate stray cancer cells. Unfortunately, chemotherapy treatments are notorious for side-effects, including extreme fatigue and hair loss.

Prospects of Nanotechnology

Development and application of nano-scaled products for cancer treatment show promise of increased efficiency with reduced, or maybe even eliminated, side-effects. Doctors and scientists throughout the country have been working on different methods for early cancer detection and elimination. Early detection of cancer cells plays a vital role in cancer prevention and treatment. Therefore, the federal government and organizations such as the National Cancer Institute (NCI) and NASA have funded the research of nanotechnology use in battling cancer [7]. With increased funding from the government and private organizations, many nanoscale devices were developed to aid in cancer detection and elimination, namely nanoscale cantilevers, dendrimers, and gold nanoshells.

Nanoscale Cantilevers

Illumin
Figure 1: Nanoscale cantilever: initial shape.
Nano-scale cantilevers resemble an everyday comb with evenly spaced teeth (Figure 1). The cantilevers possess conductive properties and are coated with specific antibodies responsive to cancer proteins [7]. Protein secreted from cancerous cells attach to the antibodies bonded to the cantilevers and actually cause the teeth to bend. This deformation creates a change in conductivity in the cantilever, alerting doctors to the presence of cancer within a patient [7]. This is much more effective than traditional detection methods because it allows doctors to detect cancer before tumor formation, and could in fact allow for the prevention of tumors if the disease is treated appropriately.

Dendrimers

While current treatments only attack the surface of cancer cells, nanoparticles bring the battle within the cancer cell. At 25-40nm, nanoparticles are capable of penetrating the membrane of cancer cells but are large enough to prevent the body from producing an immediate immunogenic response to them [8]. A special type of nanoparticle is called a dendrimer.
Dendrimers resemble spheres with tree-like branches. The tip of each branch carries a different molecule that serves a different function [9]. Thus, multiple functions can be integrated into the dendrimers to aid in the elimination of cancer cells. Dendrimers will be able to recognize and diagnose cancer cells, deliver appropriate treatment, visually identify the cells' location, and indicate the elimination of the mutated cells [10]. Use of dendrimers potentially means a one time visit for cancer patients to diagnose and eliminate cancer cells.
The dendrimers' multiple functions enable them to successfully identify only cancer cells and provide a powerful treatment that inhibits further cellular division. Recognition of and attachment to cancer cells result from the integration of folic acid with the dendrimer. Cancer cells experience a greater need for folic acid than healthy cells, thus cancer cells will attach themselves to the folic acid located at the tip of the dendrimers [11]. Once the dendrimers are attached to cancer cells, an integrated anticancer drug, methotrexate, starts to take affect. The dendrimers directly deliver the methotrexate to the tumor and destroy it without harming nearby healthy cells, unlike chemotherapy and radiotherapy, which destroy both cancer and healthy cells alike [10].

Gold-Coated Nanoshells

One of the biggest advancements in nanotechnology comes in the form of gold. Researchers have developed a 100nm diameter sphere, called a nanoshell, which consists of a silica core and a gold surface coating [12]. On top of the gold coating, the nanoshells are also coated with antibodies that recognize the Epidermal Growth Factor Receptor (EGFR) protein on the surface of cancer cells [13]. The simplistic design of nanoshells corresponds to the relatively simple chemical properties nanoshells draw on to eliminate tumors.
Gold-coated nanoshells eliminate tumors through heat rather than chemicals. Nanoshells utilize the chemical property of gold as a good heat conductor to heat tumors until they are removed. First, doctors insert the nanoshells into the bloodstream where they are able to locate cancer cells via the antibodies coated on the nanoshells' surface. A near infra-red light that induces electron oscillations at the surface of the gold-plated nanoshells is then shone over the tumor location [14]. The rapid vibrations caused by the electrons convert the light to thermal energy, which heats up the tumor and eventually eradicates it. Only 20 nanoshells are needed to completely eliminate the tumor. Nanoshells are able to target and purge only cancer cells without the introduction of chemicals into the patient's body.

Concerns about Nanotechnology

The medical use of nanotechnology does not come without its fair share of concerns. Nano-scale particles can accidentally be inhaled and ingested, where its small size allows for extreme mobility throughout the human body. Once inside, these particles can cause tissue damage or even respiratory and brain damage as the particles circulate throughout the body [15]. The ability to enter individual cells makes nanosized particles extremely dangerous.
Nano-sized particles also exhibit tendencies to alter their chemical and physical properties that differ from their regularly-sized counterparts [16]. For example, many doctors conclude that gold is non-toxic to humans due to its application in locating cancerous lymph nodes are the past 50 years [13]. However, concerns in the medical field have risen in response to the possible toxicity of gold when applied in nano-scale form, namely the gold nanoshells. Some nanotechnologies have also exhibited tendencies to clump together, thus potentially blocking vital passageways, such as respiratory and circulatory vessels [1]. The dangerous mixture of near unlimited access throughout the human body and possible unforeseen properties of nanotechnology warrants the need for these concerns and careful execution of the technology in the medical field, as well as in society.
If approved, however, there will be a widespread use of nanotechnologies battling cancer due to their predicted effectiveness and simplicity. The direct attack on cancer cells enables nanotechnology to maximize efficiency while minimizing, or even eliminating, side-effects. Projected costs of the technology, although not known at the time, should be relatively low compared to current cancer treatments since improved efficiency reduces the need for recurring treatments. Just short of being a cancer cure, these nanotechnologies will suppress and eliminate cancer cell activities more effectively, thus providing patients with a priceless peace of mind without the need to worry about cancer-related problems. Nevertheless, the key to unlocking the cure for cancer will soon be discovered as researchers dive deeper into the nanoscopic world and explore the intricate properties of and wondrous opportunities offered by nanoscale particles.

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