Nekoreguojami
2025. 01. 09
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Lithuanian scientists develop innovative nanoparticles for early diagnosis of skin cancer
Dr Martynas Talaikis, Dr hab. Gediminas Niaura, Gytautė Sirgėdaitė, Dr Sonata Adomavičiūtė-Grabusovė, and Dr Lina Mikoliūnaitė. Photo: FTMC
How can ultraviolet light, highly sensitive spectral light sensors and metal nanoparticles invisible to the naked eye be used for early cancer diagnosis? A team of Lithuanian researchers from the Center for Physical Sciences and Technology (FTMC) is ready to answer this question.
An ambitious research project is underway to develop new nanoparticles to extend the applications of a promising spectral technique that is still rarely used worldwide. This is expected to lead to more effective diagnosis of skin cancer. If successful, the results will benefit not only medicine but also other important fields, according to FTMC.
Can ultraviolet light be useful?
To better understand this topic, let's first briefly talk about spectroscopy. This is a non-destructive method which analyses the interaction of light with the material being studied. Depending on the type of spectral method used, it helps to determine the chemical composition of a material, to study interactions between molecules, and to study phase transformations or electronic properties.
(Photo: Discogs.com)
Remember The Dark Side of the Moon by the legendary Pink Floyd? Its cover shows how a glass triangular prism splits white light into different colours of the rainbow. This is just one of many results of light interacting with matter, but it illustrates this fundamental of spectroscopy.
Many different spectroscopic techniques have been developed around the world, but this time we are only interested in Surface-Enhanced Raman Spectroscopy (SERS), named after the Indian physicist Sir C. V. Raman. What is it?
The process works by placing a chemical or biological substance on a special coated metal surface, which, when illuminated by light at a certain frequency, amplifies the electromagnetic field generated by the light. This amplification significantly (sometimes more than a billion times!) increases the intensity of the so-called Raman scattering. And this is precisely the process that enables scientists to identify the molecules they are studying and understand their properties.
The SERS method uses lasers emitting visible or near-infrared light. A related technique, also being developed at FTMC, is Surface-Enhanced Infrared Absorption Spectroscopy (SEIRAS), which uses an infrared light source.
(A microscope used for surface-enhanced Raman spectroscopy. Photo: FTMC)
OK, but what does this have to do with skin cancer prevention?
"One long-standing (but so far not very successful) goal of scientists around the world has been to use surface-enhanced spectroscopy as a diagnostic method for the rapid and reliable detection of cancer spectral markers. The aim is to be able to do this even directly during surgery. A new compact device would be useful for this purpose," begins Dr hab. Gediminas Niaura, a researcher at the FTMC Department of Organic Chemistry and a laureate of the Lithuanian Science Prize.
According to the researcher, the idea was hampered by the unreliability of the method - the results were highly variable under conditions that could not be controlled: "There is quite a lot of research going on in scientific laboratories globally, but it is very difficult to apply this to clinical trials. Doctors try these technologies but stop using them because they find they are not reliable enough."
As mentioned above, surface-enhanced Raman spectroscopy uses visible or infrared light to excite spectra. However, there is an ambitious idea to apply ultraviolet laser light to this technique. This could also include the use of specially designed nanoparticles or nanostructured metallic surfaces to increase the efficiency of the SERS method. This is a new field that has not been explored much in the world and is called UV SERS for short.
How can ultraviolet radiation be superior? According to G. Niaura, many biologically important molecules absorb ultraviolet light efficiently, including molecular markers of cancer. If the laser radiation used to excite the spectra is in the ultraviolet region, the signal is significantly amplified due to a so-called resonance effect. "So by using lasers that emit ultraviolet light, we get an enhanced spectral signal from those very molecules that are cancer markers," says the FTMC physicist and chemist.
The idea of using UV SERS and specially designed nanoparticles to detect skin cancer came from discussions with Dr Tautgirdas Ruzgas, a professor at Malmö University, and a Swedish research team of his colleagues. The latter is trying to diagnose skin diseases (including skin cancer) by the relative concentration of the amino acid tryptophan and its metabolite kynurenine (a certain chemical). These biomolecules have a high absorption of ultraviolet light. With this information, the FTMC researchers decided to contribute to the development of this technique - ultraviolet spectroscopy for the detection of low molecular weight biomolecules.
The Lithuanian team working on the project includes FTMC researchers Dr Lina Mikoliūnaitė, Dr Valdas Šablinskas, Dr Martynas Talaikis, Dr Sonata Adomavičiūtė-Grabusovė, PhD student Gytautė Sirgėdaitė, and Dr hab. Gediminas Niaura (head of the project).
Their task is to create special nanoparticles (millions of times smaller than a poppy seed) for this research. What will make them special?
Particles that "give away" malignant formations
Dr Martynas Talaikis, one of the scientists involved in the project and a member of the FTMC Department of Organic Chemistry, talks about the project's ultimate goal - medical research:
"A clinical application of the method could look like this: during a health check-up, if we notice discolouration or unclear formations on the patient's skin, we place a specially prepared wet sponge on the surface of the skin, which washes away some molecules. The solution prepared in this way is examined by UV SERS and gives a quick and reliable answer."
But that's not all - for spectroscopy to work effectively, special nanoparticles need to be injected into the solution containing the skin swab sample. Their task is to interact with the molecules in the skin scrapings, which may include molecular markers of cancer. The nanoparticles would then amplify the Raman signal by illuminating the sample with a monochromatic (single wavelength) ultraviolet laser beam - and finally the scientist would analyse the sample's SERS spectrum to determine whether it contains cancerous lesions.
(Dr Martynas Talaikis. Photo: FTMC)
Here's the problem: the world hasn't yet developed high-quality nanoparticles that can do the job, so the FTMC team is looking for a way to create them. The first phase of the work is currently underway: finding suitable particles, synthesising (making) them in the laboratory and testing them on model compounds, followed by practical tests on skin samples.
"In spectroscopy in the visible or infrared, we typically use silver or gold nanoparticles, which are quite widely used around the world. However, in the ultraviolet, silver and gold are no longer suitable, and we need to look for other materials in which the surface plasmon resonance (a certain physical phenomenon) is observed in this spectral region, as this is a prerequisite for efficient Raman amplification.
These could be aluminium, copper, indium, palladium and other metals - much more "exotic" nanoparticles, as not many people in the world work with them," says Dr Lina Mikoliūnaitė, a researcher at the FTMC Department of Organic Chemistry.
(Dr Martynas Talaikis. Photo: FTMC)
The Lithuanian team is using two methods to produce the new nanoparticles. The first is purely chemical, mixing different chemicals in a solution to form the desired nanoparticles. This research is carried out in collaboration with organic synthesis expert Prof. Edvinas Orentas from the FTMC Department of Nanoengineering.
Dr Evaldas Stankevičius, an expert in laser nanoparticle formation from the FTMC Department of Laser Technologies, contributes to another method: a piece of metal is placed in a liquid and subjected to high energy laser pulses. This creates nano- and microscopic particles, which are dispersed in the solution or form nanostructures on the metal surface.
First practical tests in the summer
"There are many challenges ahead. In fact, we are already facing some," laughs G. Niaura. - There is a lot that has not been replicated that has been described in the scientific literature. For example, everybody praises aluminium particles - but we have failed in our experiments... so far. But we are moving forward. Our plan is ambitious."
If the aluminium was disappointing, other things exceeded initial expectations. For example, the researchers were very pleasantly surprised by the results of their experiments with copper. It is generally accepted in the scientific community that this metal should not be suitable for the ultraviolet region, but the FTMC team's studies using the reference biomolecule adenine have already produced promising results. This model molecule is used by many laboratories around the world and the spectral signal and other data obtained can be easily compared with the work of foreign colleagues.
A scientific paper on the viability of copper nanoparticles in UV SERS has already been written and submitted. "We have extracted these copper particles by laser and now we want to produce them chemically in solution. We are trying to create copper particles in different shapes, sizes and structures and experiment with them further. We also plan to start experiments with indium nanoparticles," says Dr Mikoliūnaitė.
(A solution containing cobalt nanoparticles is used in FTMC experiments. They are exposed to a magnet and therefore more concentrated on the right. The particles were produced by laser ablation by Dr Evaldas Stankevičius from the FTMC Department of Laser Technologies. Photo: FTMC)
The research is carried out in collaboration with photonics and nanoscience expert Dr Vladimir Sivakov from the Leibniz Institute of Photonic Technology.
In the FTMC chemistry team, each member has a different job: for example, Dr M. Talaikis performs spectroscopic studies, Prof. Valdas Šablinskas analyses and summarises spectral data, prepares scientific publications, develops vacuum evaporation of metals in order to form special plasmonic layers, suitable for UV-SERS spectroscopy, Dr Sonata Adomavičiūtė-Grabusovė uses spectral methods to characterise synthesised materials, and Gytautė Sirgėdaitė, a PhD student at the FTMC Department of Organic Chemistry, is working on the production of nanoparticles in solution.
"I'm currently working on the synthesis of copper structures using microwave methods, which is also quite new. We have a special reactor where the solution is exposed to microwaves. Very quickly, within a couple of minutes, the temperature rises to 200 degrees, and then the processes take place, with the end result being the desired new structures.
As for the copper particles, we extract them in this reactor by preparing a copper salt solution," explains G. Sirgėdaitė.
The FTMC team is the only one in Lithuania to carry out this type of research. A year on from the start of the project, the nanoparticles are scheduled to be presented to researchers at Malmö University this summer to be tested on real skin samples.
"We are now at the stage of scientific creation under laboratory conditions. Yes, our goal is ambitious and we hope to contribute to medical skin research. But if successful, the results will be useful for much broader applications. High-quality nanoparticles tailored to ultraviolet light could be used to detect pesticides, plastics, explosives, food quality research and other relevant applications," G. Niaura hopes.
Written by Simonas Bendžius
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