Scientists from the Urals Federal University and the Urals branch of the Russian Academy of Sciences have created new fluorescent chemical compounds (fluorophores) for photodynamic therapy of cancerous tumors, the latest method of treating the cancer. The compound is suitable simultaneously for the diagnosis of tumor processes by staining the affected tissues and for their further treatment by destroying tumor cells without harming healthy cells. The results of the primary studies were published in the Dyes and Pigments log.
The synthesis of these fluorophores is characterized by low cost, due to the availability of all derivatives in the composition, as well as the absence of impurities that can cause side effects. The effectiveness of the fluorophore was tested on HeLa cells used as a model of cervical cancer. Now scientists are testing how the new compound interacts with other types of cancer cells.
Fluorophores are chemical compounds that emit visible light (photoluminescence) when exposed to ultraviolet or visible light. They are able to spread through biological tissues and stain cells prone to inflammatory processes. Thus, a new compound interacts with biomolecules of body tissues and, under UV or visible irradiation, colors the areas in which the tumor growth process takes place. This makes it possible to determine the size of the tumor in the body and to define its boundaries. During the experiments, scientists found that the new fluorophore performs a dual function: it not only stains diseased areas, but also begins to destroy them.
Initially, we only studied the tinctorial properties of the compound. The compound is able to accumulate in certain areas of the cell – the cell membrane and the reticulum (an intracellular organelle responsible for protein folding), and under ultraviolet or visible irradiation highlights the infected areas in bright green. However, it turned out that the fluorophore then functions as a photosensitizer. That is, under the influence of optical irradiation, it begins to interact with the surrounding cellular environment (oxygen, water, etc.) and generates free radicals, the so-called reactive oxygen species . These active particles enter into chemical interaction with the affected cells, starting their destruction, while practically not affecting healthy cells. It’s called photodynamic therapy, it’s a promising new method of treating cancer with high efficacy and minimal side effects.”
Grigory Zyryanov, co-author of the study and professor of the department of organic and biomolecular chemistry at UrFU
Scientists using the methods of heterocyclic chemistry created two experimental samples. Chemists synthesized a fluorophore based on naphthoxazole, an oxazole derivative used in the synthesis of medicinal and biochemical preparations, and a naphthalene fragment used as a platform and so-called antenna for more efficient perception of optical irradiation by a molecule. Additionally, the chemists added fragments of pyrene and anthracene, polynuclear aromatic hydrocarbons with a high fluorescent response, i.e. a bright glow, to the compound. The compound containing pyrene showed the highest fluorescent and anticancer activity.
“Pyrenes are very commonly used for bioimaging, anthracenes are less common,” says Grigory Zyryanov. “These compounds are promising for many reasons, including we were able to show that the pyrene-containing compound begins to glow even when irradiated with visible light, and this is visible even to the naked eye. This is very practical, including, for example, for surgical interventions, when it is still necessary in the treatment.”
Slovenia, NV, et al. (2022) Synthesis of new polyarene-substituted water-soluble naphthos[1,2-d]oxazole-based fluorophores as fluorescent dyes and biological photosensitizers. Dyes and Pigments. doi.org/10.1016/j.dyepig.2022.110410.