27 February 2012

The Nanomedical Revolution

Five recent advances in nanomedicine

The article by Julian Taub The Smallest Revolution: 5 Recent Breakthroughs in Nanomedicine is published in the Scientific American Blogging Network.
Translated by Evgenia Ryabtseva

Nanotechnology is an advanced achievement in the fields of science and engineering at the same time. It is not a single field, but the result of intensive interaction between disciplines devoted to manipulations with substances at the molecular and atomic levels. In cases where this technology is used for medical purposes, the results obtained are most impressive, because they give new opportunities to improve our lives with the help of radically new approaches. This article describes five nanomedical achievements of the past year, as well as the researchers behind them.

Diagnosis of lung cancer in the early stages We are constantly confronted with images of lung cancer in social advertising dedicated to the fight against smoking.

Besides these disgusting images, there is another reason for fear: until now, lung cancer has been almost impossible to detect in the early stages. Thousands of people live their daily lives, unaware that tumors are forming in their bodies.

The screening test for lung cancer, developed by Dr. Michael Wang and biomedical equipment engineer Dr. Li-Qun Gu from the University of Missouri, is based on a simple but effective method based on the fact that when a cancerous tumor begins to form in the lungs, it violates the sequence of nucleotides in microRNA molecules. If the researcher is able to detect errors in the microRNA, he can diagnose cancer in the patient. To do this, he takes a sample of microRNAs (which are easily isolated from a blood plasma sample) and passes it through a nanopore – a hole in the protein membrane, the diameter of which is so small that it ensures the passage of nucleotides one at a time. Passing the sample through the pore, the device registers the signals emitted by the nucleotide bases during chemical interaction with the pore protein, which makes it possible to register any violations of the nucleotide sequence. The test is so simple that it allows you to diagnose the patient during his first visit to the doctor.

Dr. Wang is a professor of clinical and molecular genetic pathology at the University of Missouri. He also works at the Ellis Cancer Center, Columbus, Missouri. Dr. Gu is developing biomedical equipment at the Dalton Center for the Study of Diseases of the Cardiovascular System. The prototype for the development was the process of passing ions through cell membranes. He is working on creating similar structures that would perform important tasks for a person.

Detection of the influenza virus using gold nanoparticlesMost modern flu virus tests either require a lot of time or provide very inaccurate results.

The most accurate method is PCR (polymerase chain reaction), during which a sample is taken, stored for several days, the RNA contained in it is replicated, after which, two weeks later, the result is obtained. By this time, it may already be too late for attempts to prevent an epidemic.

However, when using a test based on gold nanoparticles, the results can be obtained immediately, and the patient can be immediately prescribed adequate treatment, which will prevent the transmission of the disease to more people. Created by a group of scientists from the University of Georgia, working under the leadership of Ralph A. Tripp, the test is based on the ability of gold nanoparticles to scatter light differently depending on their geometric shape. Researchers have created complexes of nanoparticles and antibodies that selectively bind to flu virus particles. When nanoparticles surround the virion, their geometry changes, which changes the nature of light scattering and indicates the presence of a virus. All the therapist has to do is just mix a sample of biological fluid with a solution containing gold nanoparticles. In the presence of a virus, the nature of light scattering by the solution will change greatly. The test is not only instant, but also very cheap. The amount of gold required for its holding is so small that its value does not exceed a hundredth of a cent.

In addition to determining the flu virus, this test can be used to diagnose a huge number of other diseases. Researchers can combine nanoparticles with any necessary antibodies. Antibodies of each type have special receptors that selectively bind to a specific pathogen. The test can even be used to detect salmonella in chicken meat.

Dr. Trip, the leader of the group that made this breakthrough, is working on advanced solutions in the fight against infectious diseases, such as RNA silencing, as well as on the development of a vaccine against avian influenza. He strives to understand how the cell reacts to infectious agents and how best to fight diseases.

The Sandia Cancer HuntersIn some cases, malignant tumors can be surgically removed, but often the affected cells are located in inaccessible places.

To destroy them, chemotherapy or radioactive radiation is used, but both of these methods affect not only sick, but also healthy cells. In the arsenal of oncology, there are still too few means of targeting only cancer cells.

Perhaps such a weapon was invented quite recently. The protocell created by Jeff Brinker and his team working at the National Laboratories of Sandia, New Mexico, is a clever invention that allows delivering nanoparticles filled with toxins and RNA silencers to cancer cells. It is a capsule made of porous silicon dioxide, covered with a double layer of lipids. When approaching a cancer cell, the proteins of the protocell bind to the receptors of the tumor surface, which leads to its enveloping by the membrane of the tumor cell. As a result, the protocell penetrates into the cancer cell and moves in its cytoplasm inside the membrane vesicle – the so-called endosome. To inflict a fatal blow, fusogenic (from Lat. fusio – fusion) peptides attached to the outer surface of the protocell make pores in the endosome through which hydrogen ions rush into the bubble. The pH level inside the endosome increases, which leads to the release of toxins and its rupture. Toxins spread around, poisoning the tumor and suppressing the synthesis of its proteins. Some toxins have polynucleotides attached that interact with transport RNAs that carry them to the nucleus, where they can destroy tumor DNA.

Protocells selectively act on cancer cells; their affinity (degree of binding) with an excessive number of receptors characteristic of the membranes of such cells is at least 99%. They are highly specialized and economical – one protocell is enough to suppress the vital activity of one tumor cell. They are highly stable in the liquid environment of the body, do not release nanoparticles into healthy tissues and are easy to prepare. The researchers only need to incubate the protocell in a solution containing nanoparticles and toxins that they intend to use.

There is an equally outstanding person behind this outstanding invention. Dr. Brinker is one of the researchers who seem to have come out of science fiction films. His parents did not go to college, and the impetus for choosing a scientific career was a chemistry set. Working as an intern at Sandia, he solved a scientific problem concerning aerosol gels, became a recognized expert in this field, and then wrote a textbook on the relevant subject. He is at the forefront of the work devoted to the self-assembly of molecules, the creation of new methods for the formation of porous nanostructures similar to those used in the creation of a protocell. He also created nanosensors consisting of cells immersed in nanostructures that change color under the influence of toxic materials.

Cellular feedbackUsually, in order to introduce a new drug to the market, pharmaceutical companies spend about twelve years and more than $ 800 million on the whole process.

They conduct various stages of testing, ranging from cell cultures to animal testing and, ultimately, clinical trials. However, there was always one crucial stage of testing that they were not able to carry out: testing the cellular response to the drug from the inside.

Professor Karen Martinez from the University of Copenhagen and her group have made a breakthrough in the development of biosensors. They introduced semiconductor nanotubes into the cell without changing the processes taking place in it and without killing it. Human liver cells and rat neurons were placed on indium-arsenic tubes, after which the cells remained functional and viable for several days. Having done this, the researchers evaluated the activity of processes occurring inside the cells in real time, including reactions to stimuli and the potential of the cell membrane. They could also transfer microscopic amounts of drugs through nanotubes inside the cell and evaluate the reaction of the cell from the inside.

The ability to insert electronic devices into the cell without disrupting its vital activity opens up a new area of drug testing. Now researchers can test drugs on individual neurons and receive feedback reflecting the interaction that is taking place. This technique can be used for any new drug, it can help explain the side effects associated with it, as well as improve existing drugs.

Martinez started working at the University of Copenhagen after participating in research work in Switzerland, where she studied protein receptors in order to develop more effective drugs. In addition to conducting training courses on bionanotechnology, she is a member of the board of directors of inXell, which she founded together with two colleagues who worked with her on a project dedicated to nanowires. inXell will represent the commercial side of this breakthrough. The aim of her work will be to create microchips for testing new drugs on cells, which will be based on feedback nanotechnology.

Spinal Cord RestorationEvery year, a large number of accidents occur, leaving their victims paralyzed and confined to wheelchairs for the rest of their lives.

With spinal cord injuries, cysts can form that block the regeneration process of damaged nerve tissue. Nerves located below the injured site remain cut off from the nervous system and atrophy. One of the most famous examples is the late actor Christopher Reeve. Many people see the solution to the problem of rehabilitation of patients with spinal cord injuries in the use of stem cells, but two researchers from Milan have applied a different approach.

Fabrizio Gelain and Angelo Vescovi have designed nanotubes filled with self-assembling peptides designed to provide structural support to damaged areas of the spinal cord. They tested the procedure on rats. The experiment consisted in the introduction of nanotubes into the damaged spinal cord, in which the formation of cysts took place. The analysis carried out six months later showed the absence of cysts, in place of which there was tissue formed by new cells, including neurons, blood vessel cells and osteocytes. Neurons were also found inside nanotubes previously filled with peptides. After the restoration of the damage zone, the biodegradable nanotubes should decompose without a trace.

Testing of the rats' motor abilities demonstrated an improvement in the mobility of the back and paws, while the animals no longer dragged their hind legs. They also responded to electrical stimuli better than control group animals that had not undergone therapy.

Jelain is the Vice Director of the Center for Nanoscience and Tissue Engineering in Milan. His work is aimed at creating nanomaterials designed to repair nerve tissue damage in patients with spinal cord injuries and strokes. He was a visiting professor at the Massachusetts Institute of Technology and is currently the editor of the journals PLoS One and Frontiers in nanotechnology.

Vescovi is one of the leading Italian researchers in the field of stem cells, studying the regulation of cell growth. His work is devoted to neural stem cells and the possibilities of their use for the treatment of various diseases. He is currently the director of the Italian Consortium for the Study of Stem Cells and previously worked as a consultant on stem cells at the Pontifical Academy of Life in the Vatican.

The innovations listed in the article are just the beginning of the changes that nanotechnology can bring to the quality of our lives. Its constituent industries are so extensive that the interweaving of various disciplines allows you to constantly make completely unpredictable discoveries. Where will nanotechnology take us? Most likely, no one knows this at the present stage, but the adventure promises to be exciting.

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