The Nano-War on Cancer Scientists who work on cancer research have long struggled with a painful choice: If they make the treatment powerful enough to have a fighting chance at destroying cancer cells, it is likely to destroy the surrounding tissue. But if the treatment isn’t strong enough, the cancer cells will survive and possibly spread.
Now, nanotechnology is offering hope for new treatments that overcome this dilemma. Nanotech is the science of working at an incredibly small scale; a nanometer is less than one-ten-millionth of an inch. Evidence is mounting that cancer treatments based on nanoparticles can target cancer cells with a degree of precision that was unthinkable just a few years ago.
Researchers are making progress along several paths simultaneously. Let’s take a look at some of the most promising new developments.
At Yale University, researchers led by Professor W. Mark Saltzman have developed an innovative way to deliver cancer-fighting drugs to brain tumors by injecting therapeutic nanoparticles into the brain with a catheter, and then using pressure to guide them to the tumor.1
As reported in the journal Nature Materials,2 the nonviral nanoparticle developed at Yale is able to act like a virus to introduce a specific gene into diseased cells in order to kill or repair them.
This is a big improvement over conventional nonviral gene therapy agents, which often carry a positive electric charge that can kill healthy cells. It is also safer than viral gene therapy treatments, which can cause significant immune reactions.
Saltzman’s team overcame the problem of excessive charge by making the new nanoparticle more hydrophobic (water-repellant) and thus less likely to form chemical bonds with water molecules. Specifically, the team incorporated safe, water-insoluble units into the polymer that generates the nanoparticles. This reduces the positive charge and increases stability. The result is an efficient mechanism for gene delivery that is also extremely safe.
Meanwhile, at the University of Southampton, scientists have developed smart nanomaterials that can disrupt the blood supply to cancerous tumors.
The team of researchers, led by Physics Professor Antonios Kanaras, showed that a small dose of gold nanoparticles can activate or inhibit genes that are involved in angiogenesis ? a complex process necessary for the supply of oxygen and nutrients to most types of cancer.
The team focused on endothelial cells, the cells that make up the interior of blood vessels and play a pivotal role in angiogenesis. As the researchers explained in the journal Nano Letters,3 they use a technique called laser irradiation. The team shines light on the gold nanoparticles with a laser beam, which is able to destroy the endothelial cells and cut the blood supply to the tumor.
Researchers at Cornell University are using a similar approach.4 Led by Professor Carl Batt, the researchers synthesized nanoparticles made of gold sandwiched between two pieces of iron oxide. They then attached antibodies, which target a molecule found only in colorectal cancer cells, to the particles. Once bound, the nanoparticles were engulfed by the cancer cells.
To kill the cells, the researchers pointed a laser at the nanoparticles. The gold in the nanoparticles absorbed the radiation from the laser, which caused the cancer cells to heat up and die. As described in the journal Nanotechnology,5 the surrounding healthy tissue was not harmed.
The researchers are now working on a similar experiment targeting prostate cancer cells.
Of course, there’s one shortcoming to techniques using lasers: If the cancer occurs in a place where a laser can’t reach, it won’t work. To remedy that problem, scientists at the Georgia Institute of Technology have coated gold nanoparticles with a chemical that brings them inside the nucleus of the cancer cell and stops it from dividing.
In the Journal of the American Chemical Society,6 Professor Mostafa El-Sayed, director of the Laser Dynamics Laboratory at Georgia Tech, explains that once a cancer cell stops dividing, apoptosis sets in and kills the cell. According to El-Sayed, “In cancer, the nucleus divides much faster than that of a normal cell, so if we can stop it from dividing, we can stop the cancer.”
The researchers tested the hypothesis on cells harvested from cancer of the ear, nose, and throat. They decorated the cells with a peptide called RGD to bring the gold nanoparticles into the cytoplasm of a cancer cell. They also used a peptide called NLS to bring the gold into the nucleus.
Previous studies had shown that just delivering gold into the cytoplasm has no effect on the cancerous cell. The new study revealed that implanting the gold into the nucleus effectively kills the cell.
The gold works by interfering with the cells’ DNA, although the researchers aren’t sure exactly why it works. That will be the subject of another study.
What matters is that it works ? and it works even on cancer cells that can’t be reached with the laser.
Another i
ngenious method involves heating gold nanoparticles with alternating magnetic fields rather than with a laser. At the University of Georgia, scientists have found that head and neck cancerous tumor cells in mice can be killed in half an hour without harming healthy cells.
The findings, published recently in the journal Theranostics,7 mark the first time to the researchers’ knowledge that this cancer type has been treated using magnetic iron oxide nanoparticle-induced hyperthermia, or above-normal body temperatures, in laboratory mice.
The team, led by Assistant Physics Professor Qun Zhao, found that the treatment easily destroyed the cells of cancerous tumors that were composed entirely of a type of tissue that covers the surface of a body, which is also known as epithelium.
For the experiment, Zhao injected a tiny amount of nanoparticle solution directly into the tumor site. Next, he placed the mouse in a plastic tube wrapped with a wire coil that generated magnetic fields that alternated directions 100,000 times each second. The magnetic fields produced by the wire coil heated only the concentrated nanoparticles within the cancerous tumor, and left the surrounding healthy cells and tissue unharmed.
Similarly, Virginia Tech researchers are investigating the use of magnetic fluid hyperthermia to heat and destroy cancerous cells.8 The procedure has been used successfully in prostate, liver, and breast tumors.
According to the researchers, who presented their findings at a recent meeting of the American Physical Society Division of Fluid Dynamics, they injected magnetic nanoparticles into the body intravenously. The nanoparticles then attached to the cancerous tissues. When the researchers added a high-frequency magnetic field for 30 minutes, the particles heated up, raising the temperature of the tumor cells.
Just as in the other studies, the heated cancer cells died, with no adverse effects to the surrounding healthy tissue.
To further perfect the technique, graduate student Monrudee Liangruksa and her colleagues tested the effects of different types of magnetic nanoparticles. The most promising varieties were iron-platinum, magnetite, and maghemite. But because iron-platinum is toxic to humans, the most biocompatible agents are magnetite and maghemite.
Based on this compelling research, we offer the following forecasts:
First, nanotechnology will deliver cancer therapies with unprecedented power and fewer side-effects than chemotherapy.
The success of the experiments we’ve considered, as well as several others that are similar, points to what promises to be a highly effective, precisely targeted approach to destroying cancer cells, and only cancer cells. If the results of clinical trials on human subjects, which are still years away, prove to be just as successful, we will finally have a therapy that can completely eradicate the cancer from a patient’s body ? and without the painful, debilitating side effects of current treatments such as chemotherapy. Combined with advances in gene therapy, nanotech could make the treatment for cancer as routine and effective as LASIK eye surgery.
Second, nanotech will also revolutionize medical diagnostics, with faster, more precise, and less invasive tools.
As always, a patient’s outcome will depend in part on how early the cancer is detected. With nanotech-based diagnostics, rather than waiting for weeks for a test result, doctors and patients will be able to get a diagnosis in minutes, during a single office visit. Magnetic nanoparticles will enhance today’s x-rays and MRIs, allowing technicians to find smaller tumors that would otherwise go undetected. Advances in sensors, such as a nanotech artificial nose, will enable doctors to quickly identify lung cancer in a patient’s breath in much the same way a traffic cop uses a breathalyzer to detect alcohol on the breath of an impaired driver. Doctors will be able to determine whether a tumor is benign or malignant without the pain and expense of surgery or an invasive test.
Third, nanotech-based treatments for cancer will not be available until 2018 or later.
It can take several years for the FDA to approve a new treatment to be tested on humans, and additional years before it is approved for mainstream use. One important consideration will be determining the long-term effect of gold nanoparticles on the human body.
Fourth, nanotech-based cancer treatment will have an enormous impact on healthcare costs.
According to the National Cancer Institute, almost 50 percent of Americans born today will be diagnosed with cancer at some point during their lifetimes. In addition to all of the suffering that cancer causes, it creates a financial burden on families and the overall economy. A survey by USA Today, the Kaiser Family Foundation, and the Harvard School of Public Health found that 25 percent of cancer patients use up all or most of their savings in paying for cancer treatments.9 At a national level, according to The Atlantic,10 government actuaries at the federal Centers for Medicare and Medicaid Services predict that healthcare costs ? of which cancer care is one of the largest expenses ? will reach $4.7 trillion and 19.6 percent of GDP by 2019. The New England Journal of Medicine11 reports that annual direct costs for cancer care are expected to go up from $104 billion in 2006 to more than $173 billion in 2020, due to major increases in the costs of therapy and the extent of treatment. Fortunately, those are likely too pessimistic: Once the new nanotech-based technologies are approved, earlier, faster diagnoses of cancer, followed by faster, cheaper, less harmful and more effective cancer treatments, will dramatically cut healthcare costs for individuals and eliminate much of healthcare’s drag on the economy.
References List :
1. Yale News, December 7, 2011, "Novel Nanoparticle Mimicking Virus Offers New Route to Gene Therapy," by Eric Gershon. ⓒ Copyright 2011 by Yale University. All rights reserved. http://news.yale.edu 2. Nature Materials, January 2012, Vol. 11, No. 1, "Biodegradable Poly(amine-co-ester) Terpolymers for Targeted Gene Delivery," by W. Mark Saltzman, et al. ⓒ Copyright 2012 by Nature Publishing Group, a division of Macmillan Publishers Limited. All rights reserved. http://www.nature.com 3. Nano Letters, March 9, 2011, Vol. 11, Iss. 3, "Laser-Induced Damage and Recovery of Plasmonically Targeted Human Endothelial Cells," by Antonios G. Kanaras, et al. ⓒ Copyright 2011 by the American Chemical Society. All rights reserved. http://pubs.acs.org 4. For more information about using synthesized nanoparticles to target and kill cancer cells, visit the Cornell University website at: http://www.news.cornell.edu 5. Nanotechnology, March 2010, Vol. 21, No. 10, "Gold Hybrid Nanoparticles for Targeted Phototherapy and Cancer Imaging," by Dickson K. Kirui, et al. ⓒ Copyright 2010 by Institute of Physics Publishing. All rights reserved. http://iopscience.iop.org 6. Journal of the American Chemical Society, February 10, 2010, Vol. 132, Iss. 5, "Nuclear Targeting of Gold Nanoparticles in Cancer Cells Induces DNA Damage, Causing Cytokinesis Arrest and Apoptosis," by B. Kang, M.S. Mackey, and M.A. El-Sayed. ⓒ Copyright 2010 by the American Chemical Society. All rights reserved. http://pubs.acs.org 7. Theranostics, 2012, Iss. 2(1), "Magnetic Nanoparticle-Based Hyperthermia for Head & Neck Cancer in Mouse Models," by Qun Zhao, et al. ⓒ Copyright 2012 by Ivyspring International Publisher. All rights reserved. http://www.thno.org 8. For more information about magnetic fluid hyperthermia as a cancer treatment, visit the Virginia Tech website at: http://www.vtnews.vt.edu 9. To access the report "National Survey of Households Affected by Cancer," visit the Kaiser Family Foundation website at: http://www.kff.org 10. The Atlantic, September 16, 2010, "No Cure for the Cancer of Health Care Costs," by Ben W. Heineman, Jr. ⓒ Copyright 2010 by The Atlantic Monthly Group. All rights reserved. http://www.theatlantic.com 11. The New England Journal of Medicine, May 26, 2011, Vol. 364, No. 21, "Bending the Cost Curve in Cancer Care," by Thomas J. Smith, M.D. and Bruce E. Hillner, M.D. ⓒ Copyright 2011 by the Massachusetts Medical Society. All rights reserved. http://www.nejm.org
