This is an article published by Nanotsunami in 2005.
The Importance of Using Rodents
in the Nanomedical Research
The use of minor species for the benefits of mankind always has been a controversial topic in modern society. Especially the use of animals for medical research, which is seen by some as a necessary evil in the name of scientific advance while others may think it is probably one the greatest sins mankind can commit against other species. Without entering in a profound ethical debate about the need of using other species for medical research, this article explores the importance of using rodents to study the positive and negative effects nanotechnology can have on the health of both humans and animals. Nanotechnology can have applications in various areas of human and veterinary medicine as in, for example drug delivery, drug discovery and development of diagnostics and medical devices. These applications can bring us a new era of preventive medicine, where the treatment of diseases could be initiated even before the first symptoms occur. In this article the word “rodent” specifically refers to the group of small mammals commonly use in animal research, which includes the rats and mice. Why rodents are important to the nanomedical research? The use of this group of small mammals will certainly have profound implications for curing both human and companion animal diseases. Thanks to new advances in the study of animal genetics, we know that the genome of rodents and humans are very similar. Of the thirty thousands genes possessed by a mouse, ninety-nine percent have obvious counterparts in the human genome. It is this kind of similarity that makes rodents so important for the study of the medical applications of nanotechnology.
Animal research has played a vital role in virtually every major medical advance of the last century for both human and animal health. Practically every present day protocol for the prevention, control, and cure of disease and the relief of pain is based on knowledge attained through research with laboratory animals. Thanks to the use of laboratory animals, modern medicine has boosted the average life span of Americans by almost thirty years. Animal research has also resulted in many remarkable life saving and life-extending treatment for companion animals, wildlife and endangered species. It is estimated that ninety percent of the animals currently use for medical research are rats and mice. Rats and mice make good research subjects for those studying the medical applications of nanotechnology for a variety of reasons. First, they are biologically similar to humans. Second, they are susceptible to many of the same health problems as humans; and third, they have short life cycles so they can easily be studied throughout their life span or across several generations. In addition, scientists can easily control the environment around the animal, which would be difficult to do with human subjects.
The use of rodents by the nanotechnology and biotechnology industries can be of great importance to assess the potential toxicological effects of certain nanoparticles. In theory, nanoparticles can be produce from nearly any chemical; however, most nanoparticles to which human and companion animals might be exposed have been made from transition metals, silicon, carbon, metal oxides and nanocrystals. Due to their physical and chemical characteristics, nanoparticles may not be easily biodegradable or may not be able to be removed by the immune system. Inhaled nanoparticles can accumulate in the nasal cavities, lungs and brains of rats and scientists speculate this buildup could lead to inflammatory lesions in the respiratory systems, brain damage or central nervous system disorders. These kinds of studies can provide clues about potential occupational hazards in companies dealing with the production of nanomaterials. The use of rodents will not only be crucial to design adequate safety tests and to establish proper safeguards in the work place, but will also make an important contribution to the development of a sustainable and safe nanotechnology.
Besides toxicology studies, rodents are also major contributors to other medical applications of nanotechnology. The first implantable medical device using a combination of microtechnology and nanotechnology was tried on diabetic rats. This medical device consists of a silicon box a tenth of a millimeter across, which interior contains collagen tissue seeded with pancreatic cells. The silicon box is porous with holes twenty nanometers wide that can permit glucose molecules pass from the blood stream to the interior of the device without any problem. If the pancreatic cells inside the device detect too much glucose in the blood stream, they start producing insulin. The insulin molecule is small enough to pass through the pores into the blood stream lowering the glucose levels. One advantage of using a device with nanopores like the one described here is that big molecules such antibodies will not be able to reach the interior of the device so the possibility of an immune rejection to the pancreatic cells inside the device is minimal. In theory, a diabetic rat with the implanted device can survive a couple of weeks or longer without the need for insulin shots.
Natural resistance to the use of antibiotics has always been a topic of concern in both human and veterinary medicine. One of many nanomaterials that promises to be an important weapon in our constant war against pathogenic bacteria is the nanotubes. The bactericidal effects of nanotubes are due to their ability to puncture the cell membranes. Once a cell membrane is punctured, many of cell’s internal components squirts out producing the immediate death of the bacteria. To prove the efficacy of nanotubes as bactericidal agents, researchers have been experimenting with live mice infected with lethal doses of Staphylococcus aureus. The experiments shows that those mice injected with specific doses of nanotubes survive the infection while those who do not received the injection of nanotubes eventually died. In some cases, it just takes a couple of hours or less to see the positive effects of the nanotube injection. In theory, any bacteria could eventually develop resistance to a bactericidal drug made of nanotubes. But with simply doing minor modifications to the structure or composition of the nanotubes, we would be able to compensate to any drug resistance that a bacteria may exhibit.
One of the potential applications of nanoparticles is in the field of diagnostics, which have been widely demonstrated thanks in several studies using mice. The groups of nanoparticles that show applications that are more promising are the quantum dots. In one study involving mice, researchers injected human prostate cancer cells under the skin of the rodents to promote the growth of solid prostate tumors. The scientists then conjugated a group of quantum dots to a highly specific monoclonal antibody targeted to a prostate specific membrane antigen on the surface of the prostate tumor cells. When they injected the conjugated quantum dots into the circulatory system of the mice, the dots selectively accumulated at the site of the tumor through binding to the antigen target. This technique once refined may offer the potential to diagnose certain tumors faster that conventional methods commonly use today in veterinary and human hospitals.
Besides helping with the accurate diagnosis of tumors, nanoparticles can also be used in the treatment of neoplasia. Using mice infected with cancer cells scientists have shown that gold nanoparticles can help X-rays kill cancerous cells more effectively. The mice were divided into three groups. One group was treated with a salt solution containing gold nanoparticles and irradiated with X-rays. A second group received only the radiation treatment while the third group was only treated with the gold nanoparticles solution. Scientists have found that the mice treated with the combination of nanoparticles, followed by X-ray treatment have a reduction on tumor size or in certain cases the tumor was completely eradicated. In the group that only received the X-ray treatment the tumors continued to grow. In the third group, the only use of gold nanoparticles showed no therapeutic effect. The results of the study also shown that the one-year survival rate for the combined treatment was eighty-six percent, compared with twenty percent for the X-ray therapy alone, and zero for the group treated with the nanoparticles alone. The success on the group treated with gold nanoparticles and X-rays is due to the fact that gold, which strongly absorbs X-rays, tends to selectively accumulates in tumor instead than in normal tissues. This behavior of the gold nanoparticles opens the way to new possibilities for cancer treatment.
These are only examples of the potential benefits of using rodents in medical studies dealing with the use of nanotechnology. With the advances in this field is expected an increase in the amount of rodents to be use for testing of new drugs or medical procedures. We cannot forget that besides the use of these tiny creatures, there is other alternatives to animal testing that may provide us with faster results at lower costs. These include bacteria and cell cultures, chemical tests, computer models, and advanced statistical methods. Utilization of these methods and better analysis of test results can help the nanotechnology and biotechnology industries to reduce the number of rodents needed for many experiments. It would be nice if researchers avoid the use of animals when it is possible to do while continuing with the search for alternative methods of testing the possible medical applications of nanotechnology. However, the use of rodents is going to remain an essential part of the nanomedical research because nothing can substitute for the complex functions of the whole living animal. New drugs and medical procedures that derivates from the nanotechnology research must still evaluated in animals before they can be used on human patients. For these reasons, next time you take a look of that cute long tailed mice at you near pet shop or while on the store looking for the best rodenticide that can get rid quickly of those pesky critters in your basement, just remember that thanks to them you may be able to live a longer, healthy and productive life.
Dr. Jose Feneque, DVM, received his Bachelor of Science degree in Animal Industry at the University of Puerto Rico in 1991 and his Doctorate in Veterinary Medicine at the University of Georgia in 1996.
He practices as an associate veterinarian at Crossroads Animal Hospital in Miami, Florida and is a member of the Science Advisory Board for the Nanotechnology Development Corporation.
His special interests include the veterinary applications of nanotechnology, veterinary pediatrics, soft tissue surgery and internal medicine.
He can be contacted by phone at (305) 279- 2000 or via email at firstname.lastname@example.org.
Copyright © 2005 Jose Feneque