by Peyton K.
Cancer is perhaps the most long-standing disease that still lacks adequate treatment. The National Cancer Institute estimates that 1,660, 290 Americans will be diagnosed with cancer and 580,350 Americans will die from cancer in 2013 alone. However, developments in the field of nanotechnology are showing great promise in fighting cancer. Recent breakthroughs in the field of nanotechnology offer tremendous improvements in diagnostics and treatments of all types of cancer and could potentially lead to an effective, timely treatment with little to no side effects (National Cancer Institute nd).
All of the imaging methods currently available, such as MRI or CT scans, are only able to detect cancer cells that have proliferated to the point to cause tissue damage. Nanotechnology can target pre-cancerous and cancerous cells before tissue damage occurs by using a molecular marker to tag cancerous and pre-cancerous cells (Nature Reviews 2007). Nanoparticles are able to detect these cells through their antibody and metal oxide coatings. The antibody coating is capable of binding to specific receptors that are over-expressed in cancerous cells. The metal oxide coating provides a high-contrasting signal that will light up cancerous cells once the antibodies bind so that MRI or CT scans can identify them. The ability to detect cancer in it’s earliest stages allows physicians to begin treatment earlier than we are currently able to. This is a huge advantage because studies have shown that the patient outcome and chance for recovery is exponentially better the sooner treatment begins. (National Cancer Institute nd).
Nanotechnology also offers numerous benefits for the treatment of cancer. The goal of nanotechnology is to target and destroy cancerous cells while not affecting healthy tissues. When researchers first began to apply nanotechnology to cancer, the ability to effectively target the appropriate cancerous tissue was a major concern. Initially, the risk that nanoparticles could also invade healthy tissue seemed high. George Whitesides, professor of chemistry and chemical biology at Harvard University, voiced this concern and stated he believed that research should focus on using nanoparticles in diagnostics, not treatment. “Cancer cells are abnormal cells, but they’re still us,” he said, “It’s easy to say that one is going to have a particle that’s going to recognize the tumor once it gets there and will do something that triggers the death of the cell, it’s just that we don’t know how to do either one of these parts” (Maynard 2010).
Luckily for the supporters of nanotechnology, recent developments have vastly improved the accuracy of the targeting of nanoparticles. Currently, both passive and active targeting techniques provide effective means of guiding nanoparticles to cancerous cells and protecting healthy tissues. Passive targeting takes advantage of the increase in angiogenesis, or growth of new blood vessels, caused by tumor formation. When the cancerous cells that make up a tumor begin to proliferate at high rates they require an exponentially higher amount of nutrients than the circulatory system delivers, so the tumors stimulate rapid angiogenesis. Because the new blood vessels are created rapidly, they are generally weaker and “leakier” than normal blood vessels. Currently, researchers are working with creating nanoparticles of 10-300 nm in size filled with the cytotoxic drugs used in chemotherapy to take advantage of these “leaky” new blood vessels. These nanoparticles will only be able to leave the blood vessels at the sites of angiogenesis around the tumor because the pores in a normal blood vessel are around 2-4 nm so the healthy tissues remain unharmed (Grossman and McNeil 2012). The National Cancer Institute defines active targeting of nanoparticles as “actively targeting drugs to cancerous cells based on the molecules that they express on their cell surface”. In active targeting, a nanoparticle is coated in a molecule that binds to receptors only found on cancerous cells. The ultimate goal of active targeting is for the nanoparticle to bind to a receptor on the cancerous cell and induce the cell to absorb the nanocarrier. Once the nanocarrier is inside the cell, an external stimulus such as a pH level change would stimulate the nanocarrier to release its cytotoxic drug and effectively destroy the cancer cell (National Cancer Institute nd).
Recently, researchers have been combining the characteristics of both active and passive targeting to further reduce the risk of nanoparticles interacting with healthy tissues with the creation of nanoshells. Nanoshells are perhaps the most exciting development of nanotechnology in relation to cancer and while nanoshells have been used extensively in laboratory and animal experiments, they have yet to be tested on humans. Nanoshells are composed of a silica core with a metallic coating and they have the capability to destroy cancerous cells from within. Once injected, the nanoshells will aggregate at the location of any tumors due to the use of passive targeting. Some nanoshells will also be coated in a layer of antibodies capable of binding to antigens on cancerous cells. The nanoshells will then be absorbed into tumors via active targeting. Once inside the cells, scientists apply energy, such as infrared light beams, to the nanoshells and the metallic layer absorbs the energy. The absorption of the energy creates an immense amount of heat that ultimately kills the cancerous cells of a tumor (National Cancer Institute nd).
Light-activated nanoshells have been used with great success in laboratory studies on in vitro human cells along with in mice. In a recent study, researchers applied laser-activated nanoshells to an in-vitro human breast cancer cell line. Upon using the laser to destroy cancerous cells, they found that the nanoshells “demonstrated a surprisingly well-demarcated zone of cell death, limited to the laser spot size”. The researchers also noted that the remaining non-cancerous cells remained cancer-free (Stern and Cadeddu 2008). Another study published by researchers at Rice University and the Baylor College of Medicine reports the successfully use of light-activated nanoshells to destroy the brain cancer cells associated with glioma. According to the study, half of the mice that had the treatment had all glioma tumors destroyed and remained cancer free even three months after the procedure. The success of this study is extremely valuable because glioma is an inoperable cancer with a high mortality rate (Science Daily nd).
While researchers are excited with the results of these recent studies, follow-up labs and studies are needed prior to these nanoshells being used in human trials. If nanoshell technology is proved to be safe for use in treatment, one valuable advantage it would provide would be the quick treatment time. In the study on the effect of nanoshells on glioma, the total treatment time was 24 hours as opposed to the months that patients currently endure chemotherapy (Science Daily nd).
While exciting developments like nanoshells remain in development, there are nanotechnology based medications currently available on the market called nanocarriers. Nanocarriers are defined as nanoparticles filled with a predetermined amount of a cytotoxic drug. Generally these nanoparticles are covered with a polyethylene glycol (PEG) coating and a layer of aptamers. The coating of PEG protects the nanoparticles as they travel through the circulatory system and into the tumor. Aptamers act as RNA-based targeting agents that bind to certain receptors on the membrane of cancerous cells. Inside of the layers of coating lies a cytotoxic drug, similar to those currently used for chemotherapy, like docetaxel. In a recent study, researchers injected nanoparticles with aptamers specific for the antigens of cancerous prostate cells into mice with prostate cancer and found that all cancer was completely eradicated after only one injection (Nature Reviews 2007).
The two FDA approved nanotechnology-based medications currently available on the market are Doxil and Abraxane. Because these medications target only cancerous cells and not healthy cells, they have very few of the side effects associated with chemotherapy. While the medications offer a higher quality of life for cancer patient, there is a high cost associated with the drugs. For example, the cost of Abraxane and Doxil per-dose was around $5000 in 2009 as compared to medications used in chemotherapy which range in price from $200-500 per dose. While these nanotechnology based medications do provide patients with a significantly higher quality of life, they only offer slight improvement in overall survival rates (Grossman and McNeil 2012). An advantage offered by these nanocarriers is the control they give scientists over the amount of cytotoxic drugs they wish to administer. As stated by Dr. Ferrari, professor of nanotechnology at University of Texas Health Science Center, “I believe the era of ‘rational design’ of nanoparticles has arrived” (Nature Reviews 2007).
Despite the many advantages and benefits nanotechnology has to offer, it does come with some disadvantages. A major concern with the use of nanotechnology was how to eliminate nanoparticles or nanoshells from the body once they had destroyed cancerous cells. If the nanoparticle is less than 8 nm in size, it will be able to be expelled via urine (Maynard 2010). However, the current use of passive targeting has caused nanoparticles to be created on a larger scale, often 10-300 nm in size (Grossman and McNeil 2012). Fortunately, a recent study by a team of researchers at the California NanoSystems Institute at UCLA solved this problem by successfully developing nanoshells that consist of water-soluble polymers. The water-soluble polymers allow the nanoshell to simply dissolve harmlessly into the surrounding healthy tissue once it has destroyed the cancerous cell (The Engineer nd).
Another major problem presented by nanoparticles is their characterization. A team performing studies on the safety of nanotechnology injected rats with two batches of nanoparticles. They found that one of the batches of nanoparticles a caused the rats to develop lung lesions, a result that had never been demonstrated by the particular nanoparticle before. Upon further analysis, researchers discovered that the two batches had a microscopically small difference in polymer concentration and the batch with the less dense polymer concentration was degraded over time, thus causing lung lesions (Grossman and McNeil 2012).
Another obstacle is the body’s immune system. The sizes of most diagnostic and therapeutic nanotechnologies fall within the same size range that our immune system will recognize and destroy. Martin Philber, a Senior Associate Dean at the University of Michigan states that “a major challenge is the design and fabrication of nanotechnologies that will either avoid immune cells or use them to achieve appropriate targeting without activation or suppression of immune function”. Researchers are currently applying various types of coatings to nanoparticles that will help them to go undetected by the immune system with some success (Maynard 2010).
While there are currently obstacles associated with nanotechnology, there are none capable of casting significant doubt on the use of nanotechnology. The vast amount of benefits offered by the technology is cause enough for human trials to begin and research in the field to progress. The capability of the technology to find and mark cancerous cells before any damage has occurred and to effectively destroy all cancerous cells while leaving healthy tissues untouched in a simple outpatient procedure causes researchers, physicians, and patients alike to view the application of nanotechnology in cancer as a breakthrough capable of radically changing the current diagnostic and treatments available for the better.
Grossman, J.H., McNeil, S.E. 2012. Nanotechnology in cancer medicine. Physics Today. 65:8.
Maynard, A. 2010. Nanotechnology and cancer treatment: Do we need a reality check?. 2020 Science.
National Cancer Institute. Learn About Nanotechnology. April 2, 2013.
Nature Reviews. 2007. Cancer nanotechnology: small, but heading for the big time. Nature Reviews Drug Discovery. 6:174-175.
Science Daily. 2011. Early Tests Find Nanoshell Therapy Effective Against Brain Cancer. Science Daily.
Stern, J.M., Cadeddu, J.A. 2008. Emerging use of nanoparticles for the therapeutic ablation of urologic malignancies. Urologic Oncology: Seminars and Original Investigations. 26(1), pp 93-96.
The Engineer. 2013. Nanoshells could enhance precision of cancer treatment. The Engineer.
— Peyton Kremer 2013/03/26 13:36