Nanodiagnostics and nanotherapy
How are nanoparticles used in medicine?
Andrey Zvyagin, Doctor of Physico-Mathematical Sciences, Head of the Department of Biomedical Engineering at the Institute of Molecular Medicine of Sechenov University, Professor at Macquarie University, Australia.
Post -science
What is a nanoparticle? According to the definition of metrologists, the size of a nanoobject should be less than 100 nanometers. One of the paradoxical examples is a soap bubble. In fact, it is also a nanoobject: when we inflate a bubble, it changes color, and its walls darken, becoming almost invisible. As it was proved by optical scientists, at this moment its wall thickness becomes less than 100 nanometers, and thus it is nanoscale. However, much more often scientists in the life sciences deal with nanoparticles in the form of round or elongated balls. So nanoparticles have found an important application in oncology: they help to detect malignant tumors, deliver drugs to them and defeat them.
The main part of drugs in oncology is classical chemotherapy. Doctors inject chemotherapeutic drugs, which are essentially poisons, intravenously, and they spread throughout the body, penetrating into tissues and poisoning them. Chemotherapy affects not only cancer cells, but also healthy tissues, and this is a serious problem that nanoparticles can help solve.
Nanoparticles do not get into most of the tissues: they cannot go beyond the walls of healthy vessels. However, tumor tissues have increased vascular permeability, and nanoparticles can penetrate them, which was proved by Japanese pharmacologist Hiroshi Maeda in the 1980s. But the immune system quickly removes nanoparticles from the bloodstream. This is also a serious challenge for scientists.
Why nanoparticles are better than traditional cancer drugs
The advantage of using nanoparticles in chemotherapy is undeniable: they are less toxic than standard drugs. For example, doxorubicin is an antitumor drug that damages the DNA of cells. The smooth muscle cells of the heart are the most sensitive to it. Under the influence of doxorubicin, the rhythms of the heart change, which can lead to heart failure or arrhythmia. If doxorubicin is administered as part of nanoparticles, its concentration in the body will be higher, but it will not cause serious complications.
Thanks to nanoparticles, the side effects of chemotherapy have significantly decreased, despite the fact that they are not inferior in effectiveness to standard drugs. Today, many scientific groups are trying to assemble their own complexes – complex nanoconnections that will have amazing properties and significantly simplify cancer therapy. For example, it is possible to make nanocomplexes that will self-destruct when they get into a tumor. This will facilitate the spread of the drug throughout the entire volume of malignant formation. They can be made contrasting, distinguishable by existing medical imaging systems, such as MRI, CT, ultrasound, as well as optical systems – the latter has found wide application in working with oncological animal models to study oncotherapy methods. Nanocomplexes can be made hybrid, combining organic and inorganic nature. Biohybrid complexes can be created in such a way that they are able to avoid capture by cells of the immune system, which will lead to better accumulation in tumors and metastases. And this is only a small part of the opportunities offered by nanotechnology.
How nanoparticles will help protect from the sun
Another area where nanoparticles are used is toxicology. People inhale, consume particles of various substances and come into contact with them. However, not all particles from this variety are safe, some can seriously harm a person. The effect of nanoparticles on our body and possible approaches to reducing their effects are being studied by nanotoxicology.
The simplest example is sunscreen. You came to the beach and, to protect yourself from ultraviolet rays, applied a cream to your skin. It would seem that what could threaten? The fact is that the nanoparticles of the cream can penetrate into the skin cells and damage them. Nanoparticles of organic filters, for example, octocrylene or ensulisol, are particularly distinguished. They discolor under the rays of the sun, like clothes, and lose their protective properties, so the cream has to be applied repeatedly. Organic matter can also lead to unpleasant consequences, such as skin irritation.
Not only organic compounds are used in sunscreens. In most modern products, the main component is inorganic particles, namely zinc oxide and titanium dioxide. These two metal oxides are good because they are photo-resistant, do not break down under the influence of sunlight. However, they also have their disadvantages: under the rays of the sun, they become photocatalysts and begin to produce active radicals, which are safe because they remain in the cream.
Zinc oxide nanoparticles are considered the most effective sunscreen filter. They absorb light in a dangerous range – ultraviolet type A, which can lead to burns of varying degrees and damage DNA. As a result, a person may have mutations that lead to the development of melanoma – a malignant formation.
But in 2016, in a scientific article (Holmes, A.M., et al., Relative penetration of zinc oxide and zinc ions into human skin after application of different zinc oxide formulations. ACS nano, 2016) a message appeared that zinc particles, once on the skin, dissolve and enter the body. The stratum corneum of the epithelium – the upper layer of the skin – is acidified by the secret of the sebaceous gland, which protects it from microbes. As it turned out, nanoparticles dissolve in secret and penetrate into cells as ions.
Cellular machinery is based on the fact that zinc is involved in cell regeneration and wound healing. But will the extra zinc that penetrates the skin after sunscreen be toxic to the body? We have been working on this issue for many years in the laboratory of Macquarie University (Australia) and Sechenov University, and now we are preparing the research results for publication.
Why is this issue so important? The sun's rays cause skin cancer. This is especially true for those who spend a lot of time under the sun. For example, two out of three Australians born in this country will be diagnosed with some form of skin cancer by the age of seventy. Not all types of skin cancer are as malignant as melanoma, but I would like to protect myself from all. That is why a public campaign has been launched in Australia against this form of oncology. Skin cancer occurs when cells are damaged as a result of excessive exposure to ultraviolet radiation from the sun. To protect people from melanoma, pharmaceutical companies are developing new compounds for sunscreens, including based on the latest advances in nanomedicine.
Diagnostics, therapy and application of nanoparticles
In addition, nanoparticles are used in theranostics, an approach in medicine that combines therapy and diagnostics. The main area in which theranostics is involved is oncology. Suppose a cancerous tumor is difficult to detect. In this case, nanoparticles will help us. When nanoparticles are injected into the body, the substandard formation accumulates them. To detect it, scientists make nanoparticles capable of contrast – distinguishable imaging tools, including MRI, CT, ultrasound, as well as optical cameras. In the latter case, registration occurs as follows: when the necessary amount of such particles has accumulated in the tumor, they are irradiated with light, which the nanoparticles re-emit with a change in color, and they can be registered using, for example, a camera. This method is called fluorescent imaging, and it allows you to detect oncological diseases, as well as detect and remove malignant tissues remaining after surgery.
But there are more standard methods, for example, radioactive imaging. Radioactive tracers are introduced into the body – special nanomaterials that are used to monitor a chemical reaction or biological process. Thanks to imaging systems, it is possible to detect a tumor. Magnetic particles of iron oxide are also used: they accumulate in tumors, and in MRI systems, the places of clusters are visible. This is how you can detect a tumor and its accompanying metastases. These methods are currently in active development, and there is reason to believe that they will be used in clinical practice.
Theranostics is applied to humans, but nanoparticles are involved less than standard drugs. One example of theranostics, if not tied to nanoparticles, is visualization during surgery to remove glioma, a brain cancer. Glioma is formed in such a way that the node is visible, but filamentous metastases that penetrate into the brain tissue are not. These metastases must be removed: if this is not done, the tumor may develop again. To understand where the metastases and the tumor itself are located, fluorescent markers are injected into cancer tissues.
One of these fluorescent markers is the drug alacens, which is used for the treatment and diagnosis of oncological diseases. It accumulates in tumor cells and causes them to produce porphyrin, a pigment that is widespread in large quantities in wildlife. Porphyrin is valuable because if you shine a green light on it, it will glow red, which indicates the potential of the pigment in medicine. It is enough for doctors to put a filter that blocks green light and a filter that highlights red. Thus, during the operation, the surgeon does not look at the tumor, but at the monitor, on which the malignant formation is highlighted in red.
In the NMIC of Neurosurgery named after academician N. N. Burdenko, operations using alacens are carried out as standard. Alacens is a drug that allows photodynamic therapy. If you shine a strong light on it, it will be toxic to the tumor. Such an operation is possible, but surgeons prefer to operate. This is an example of how a diagnostic drug helps in human surgery.
Theranostics is actively developing, but, unfortunately, today nanotechnology has not found wide application in oncology. Scientists prefer chemotherapy in an established form, rather than using nanoparticles. One of the reasons is the long and expensive testing of nanopreparations and the approval of supervisory medical departments, which is quite reasonable: first of all, it is impossible to harm the patient. In addition, nanomedicine preparations are high-tech, and therefore expensive. Therefore, theranostics using nanoparticles is mainly used in animal studies, but such types of imaging systems are extremely useful: doctors inject the drug and see where it has accumulated. It is so easy to detect cancerous tumors and operate on a person at the right moment.
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