A project of St Petersburg University students facilitates detection of malignant tumours

Fluorescence molecular tomography is a modern method of biomedical visualisation that is gaining popularity in clinical practice. It enables monitoring of what is happening in the living organism without tissue-based biopsy.

The method is based on fluorescence, which is the emission of light by a substance that has absorbed light. It can be observed in nature, and is visible to the human eye. For example, biofluorescence is common among corals, anemones, hydroid jellyfish, copepods, jumping spiders, scorpions, cephalopods, and some species of fish and birds. Fluorescence has many practical applications, including energy-saving lighting systems and interior design, the clothing industry, and even body tattooing.

Fluorescence tomography makes use of fluorophores – chemical compounds that can absorb and emit light within a range of wavelengths. With fluorescent labels that emit light within the wavelengths near infrared region (NIR), deep imaging of live tissue is possible.

One of the main limitations of fluorescence tomography is that high resolution imaging is achievable only within the superficial layers of the tissue. The project of the Light up team is aimed at solving this problem.

‘By using silver and gold nanoparticles as the labels, we seek to amplify the fluorophore signal in the NIR window. This is where light has its maximum depth of penetration in biological tissue. These metals are used because they have proven themselves particularly successful as optical amplifiers,’ explains Aleksei Smirnov. He is the captain of the Light up team, a first-year master’s student in the ‘Chemistry’ programme, and the chairman of the St Petersburg University Photonics Society. ‘Besides, we are trying to understand which nanoparticles are more stable in an isotonic solution. In terms of the salt concentration, isotonic solutions are similar to blood. It is crucial that the nanoparticles remain stable not only in the artificially synthesised medium, but also in a living organism.’

The method can be applied for tissue analysis for ex vivo and in vivo cancer diagnosis. However, for in vivo applications, labels must first undergo multiple clinical trials.

There have been many studies on intravenous administration of silver and gold nanoparticles in the body, and, thankfully, toxicity has not been detected. Nonetheless, since there are no clinical trials data available regarding their elimination from the body, it is impossible to guarantee the absence of side effects.

The captain of the Light up team, the chairman of the St Petersburg University Photonics Society Aleksei Smirnov

Gold and silver nanoparticles are connected to delivery vectors. The latter are biologically active molecules used as carriers to selectively transfer the nanoparticles towards target cells, allowing for cell labelling.

After injection into the bloodstream, the labels are distributed throughout the body. In the tissues once they meet the target cells, they attach to them, forming an immune complex in which the antigen binds to the antibody. Thus, vectored antibodies attach to antigens on the surface of cancer cells. This enables detection of fluorescence emission that originates from a whole region of cells and facilitates the selective visualisation of live cell molecules.

If fluorescent labels are injected into a human patient, a specialist monitors the process on the screen of a fluorescence tomography scanner. In laboratory practice, plate fluorimeters and flow cytometers are used for the same purpose.

The technology proposed by the Light up team allows for amplifying the fluorophore signal tenfold. This will facilitate cancer diagnosis when the tumour is located deep in the tissues or it is small in size. Besides, signal amplification will help to reduce the number of labels for a single diagnosis, which in turn will reduce the cost of the procedure, hence increasing the procedure’s availability.

‘There are other potential applications of the method. For example, fluorescent labels can be modified for hyperthermia therapy. The idea is that in absorption of radiation, the metal nanoparticle transfers only part of the energy to the fluorophore. The rest of the energy is dissipated in the form of heat,’ explains Aleksei Smirnov. ‘Consequently, in the vicinity of the particle, the temperature rises. If it reaches 44–45 degrees centigrade, it may cause cell death. There has been a study on nanoparticle-mediated hyperthermal therapy in animals: all the study participants made a full recovery. The long term future of this technology is likely to lie in theranostics. However, thorough research into it has yet to be undertaken. Theranostics is a fashionable term derived from a combination of the words ‘therapy’ and ‘diagnostics’. It is a concept which involves the integration of diagnosis and therapy in a single platform using nanomaterials.’

According to Aleksei Smirnov, the project has no direct analogue either in Russia, or overseas. The first thing the Light up team members plan to do is try to attract foreign investors, and only afterwards enter the domestic market. The reason is that in Russia fluorescence molecular technology is far less developed. Besides, the estimated cost of their product is significantly lower than fluorophores produced overseas. The final consumers of the product are projected to be private and public medical diagnostic laboratories.

Together with Aleksei Smirnov, the Light up team united first-year master’s students, who are all working on the project: Olga Odintsova (programme ‘Chemistry’), Veronika Lashkul (programme ‘Biology’) and Ekaterina Baranova (programme ‘Master in Management’). The team’s academic supervisor is Elena Solovyeva, Associate Professor of the Department of Physical Chemistry at St Petersburg University. Also, the students have been assisted by Vladimir Sharoyko, a leading research associate at the Laboratory of Biomedical Chemistry of St Petersburg University.

In the final, we plan to present the results of the synthesis and modification of labels. Recently, we have managed to register a fivefold signal amplification with gold nanoparticles as fluorescent labels in comparison to conventional ones. Of course, this is only the first stage of the project and we will need to refine our labels

The captain of the Light up team, the chairman of the St Petersburg University Photonics Society Aleksei Smirnov

The greatest challenge for the team, according to Aleksei Smirnov, was the product market and opportunity assessment. The thing is, the project is knowledge-intensive, and it is difficult to forecast the profits it could bring. However, the project participants believe that the benefits of the project, including the potential to aid in cancer screening, diagnosis and therapy, outweigh the financial incentives.

The ‘SPbU Start-up’ contest is being held at the University for the fifth time. Teams that have presented best knowledge-intensive and commercially viable business models will receive monetary prizes from the Endowment Fund of St Petersburg University: 300,000 roubles for the first, 200,000 for the second, and 100,000 for the third place. Additionally, the two winning teams may be offered to establish a small innovative enterprise with the participation of St Petersburg University. Grants for their projects’ development will amount to 1,000,000 and 700,000 roubles for the first and second places respectively. For detailed information about the ‘SPbU Start-up – 2020’ student contest please visit the website of the Endowment Fund of St Petersburg University.

‘The “SPbU Start-up” contest is incredibly useful, especially for up-and-coming researchers in the natural sciences. We work in laboratories and periodically get interesting results that can be commercialised. The point is, at the university, we tend to acquire only theoretical knowledge in economics, while here we have to present our projects to the experts and prepare real business plans. This gives us an extremely valuable experience,’ emphasises Aleksei Smirnov.