Nanotechnology in medicine: Part 1
Nanoparticles: When it's important to be a very small creature
Anna Petrenko, Copper NewsPiglet sniffed slightly.
"It's hard to be brave," he said, "when you're just a Very Small Creature.
The rabbit, who had meanwhile started writing something, looked up for a second and said:
– Precisely because you are a Very Small Creature, you will be very useful in the upcoming adventure for us.
(A.A. Milne, "Winnie the Pooh and Everything, Everything, Everything", translated by B. Zahoder)
The words "nanoscience" and "nanotechnology", heard in the news and among grant recipients, sometimes suggest that these developments are very young.
Usually the epithets "promising", "prosperous" are applied to them, which is reflected in the financing. For example, 130 billion rubles were allocated for Rosnanotech in 2007.
The program for the development of the nanoindustry in Russia, adopted in 2008, assumed the allocation of 318 billion rubles for the development of nanotechnology until 2015.
Scientists are actively researching nanoparticles, since they are the link between matter, as it is perceived by humans, and atomic/molecular structures.
Modern knowledge about the behavior of materials at the "nano" level is compared with the tip of the iceberg and the embryonic stage. Active research in this area is only a few decades old.
Long storyIn fact, "nanomaterials" are much older than humanity.
Nanoparticles, that is, particles smaller than 100 nm, have been present on planet Earth since the first days of its existence.
Empirically, ancient artisans also reached their use. The most famous product is the Lycurgus Cup of the IV century, which is kept in the British Museum. Due to the presence of colloidal gold and silver in the glass, the appearance of the exhibit depends on the lighting. If the light falls from the outside, the Roman cup looks opaque and green, and if from the inside it looks translucent and red. In the IX-XVII centuries, metal particles were part of the glaze for ceramics, which was used in the Islamic world. They also owe their juiciness to the colorful stained–glass windows of cathedrals - for example, in Notre Dame in Paris.
Photo: archae.ru
The impact of nanoparticles on humans is not new either, not through the prism of art, but directly. It was found that after the Industrial Revolution with the advent of industrial enterprises and cars, the fogs of London contained nano- and microparticles. Thanks to them, England was dubbed the "foggy Albion". Now an unsuspecting resident of a megalopolis is undergoing an unforeseen "therapy": he inhales 107 nanoparticles in 1 cm3 of polluted air.
The first steps in biomedicineFortunately, usually the "acquaintance" with nanoparticles occurs intentionally.
Many believe that the most promising role awaits nanoscience in biomedicine – and in this area it has already borne fruit. The nanoparticle here plays the role of a "carrier" for a drug that can be injected into the body by itself. But attaching the drug to the carrier can both increase the effectiveness of therapy and reduce its undesirable side effects.
Practical developments began in the 1960s. As a direct participant in the events and researcher Jorg Kreuter writes in his review, one of the first researchers was Professor Peter Paul Speiser from the Swiss Federal Institute of Technology (Swiss Federal Institute of Technology). He and his group were the first to create polyacrylic spheres for oral use, then studied microcapsules and, finally, designed the first nanoparticles that could be used for vaccination and drug delivery. The main principle that the team eventually developed was the delayed release of the substance from the nanocapsule. In this case, the nanoconstruction could circulate through the circulatory system after intravenous administration and gradually release the drug.
The pioneers of nanoscaling faced criticism and misunderstanding from many colleagues, who thought that there was practically no use of such technology. The pharmaceutical industry also could not appreciate the advantages that nanoscience provides for a long time. "I still remember the congress of the early 80s, where I heard a comment from an industry scientist about one of my posters - he believed that the development of nanoparticles would die after my retirement," recalls Kreuter.
But this prophecy did not come true. Nanoparticles have been used in medicine and pharmaceuticals for more than forty years. Despite the fact that the behavior of nanoparticles in the body cannot always be predicted, it is possible to synthesize such particles that will predictably interact with proteins, nucleic acids, cells and tissues. The first commercial product with nanoparticles – Abraxane – appeared on the market in early 2005. It is an antitumor drug, and its composition includes serum albumin and paclitaxel. Nanoparticles have been used for the diagnosis of diseases for more than 15 years.
"Nanoscience" has penetrated even into the cosmetics industry. Titanium dioxide particles have been adopted by manufacturers of sunscreens. L'Oreal has been developing vitamin E delivery through the skin, and the Clinique brand has long had a serum with nanoparticles.
Currently, many forms of nanoparticles are being used and studied: polymer, ceramic, liposomes, iron and silver oxide nanocrystals, fullerenes, carbon nanotubes, quantum particles, etc. Separately, they are engaged in designing the surface of the nanoparticle, achieving the required flexibility and the value of the surface charge. For example, due to the presence of negatively charged groups on cell membranes, cationic nanoparticles are more easily absorbed by the cell than positively or neutrally charged ones. In turn, anionic particles most likely penetrate into the cell by pinocytosis or by diffusion through the membrane.
In addition, scientists can integrate certain molecules onto the surface of a particle and thereby determine which proteins and cells it will come into contact with after being injected into the human body.
TreatmentWhat is so good about nanoparticles as carriers of drugs?
The drug appears in the body not by itself, but attached or enclosed in a nanoparticle. This facilitates the absorption of drugs, changes their distribution through tissues, reduces metabolism and increases the penetration of drugs through biological membranes. This often reduces the toxicity of therapy and the risk of side effects.
An important property of nanoparticles is targeting. They can deliver the medicine directly to the target. Joerg Kreuter gives the history of the appearance of the term "magic bullet" in the medical sense. The concept of delivering a substance "to the address" goes back to the famous immunologist Paul Ehrlich. Once he visited the opera "The Free Shooter" by Karl Maria von Weber. In it, Dean of the characters sold his soul to the devil for magic bullets, which always never miss, even if the shooter did not shoot well or the target was out of reach. After that, the scientist formulated the principle of the medicinal "magic bullet".
The maximum benefit from obtaining a drug in a new form is achieved in the treatment of malaria, nosocomial infections – that is, in cases where therapy is toxic and dangerous to healthy tissues.
Of course, antitumor therapy occupies a special place. For example, delivering chemotherapy directly to a tumor significantly reduces damage to healthy body tissues.
Targeting can be achieved by the fact that the drug is "released" – disconnected from the nanoparticle – in a strictly defined place. This may be caused by an external stimulus or features of the diseased tissue. Thus, the design of "smart" nanoparticles minimizes damage to healthy tissues.
The pH of the external environment of cancer cells and at the site of inflammation is shifted to the acidic side, and in this case the drug is released when it enters the acidified environment. In addition, some types of tumors have specific enzymes, for example, elastase, protease, alkaline phosphatase. In this case, an enzymatic reaction occurs, as a result of which the enzyme disrupts the structure of the nanoparticle or directly cleaves off the molecule. Finally, reversible electrostatic and hydrophobic interactions of the drug and nanoparticles also serve for the controlled release of the drug.
Silver nanoparticles in mutated cells. Photo: Shutterstock
External influences include heating, irradiation of tissue with light or the use of other emitters of electromagnetic waves. You can heat a part of the tumor, and the drug from nanoparticles with a temperature-sensitive shell will be released in this place. Some magnetic nanoparticles in the electromagnetic field heat up themselves and "burn out" the cancer directly.
Detection and visualizationAn important field of application of nanoparticles is the visualization and diagnosis of disease using nanoparticles.
For example, in 2014, scientists from Imperial College London managed to improve the method of diagnosing cancer in the early stages by increasing the sensitivity of MRI scans.
The engineered nanoparticles are coated with a protein whose receptor is located on cancer cells. When ingested, the particles "seek out" the tumor and come into contact with it. This interaction destroys the coating of the nanoparticle and causes the self-assembly of the exposed nanoparticles into a larger formation. That's what doctors will be able to detect on an MRI. The development has so far been successfully tested on a mouse model.
Professor Nicholas Long from the Department of Chemistry at Imperial College says that earlier detection of a tumor, which this method can provide, will allow patients to receive effective antitumor treatment earlier and increase survival.
20.06.2015