Advanced PDT
New opportunities have opened up in overcoming the resistance of tumors to therapy
For many years, oncological diseases remain one of the most acute problems for healthcare. The observed annual increase in the number of cancer diagnoses around the world encourages scientists to research and develop new and improve existing treatment methods.
The resistance of tumors to traditional antitumor therapy is largely determined by the withdrawal of malignant cells from immunological control. Therefore, the most promising direction of increasing the effectiveness of therapy is considered to be the activation of tumor cell death by the immunogenic pathway.
"Attracting the attention" of the immune system to the tumor focus occurs as a result of the release of molecules associated with danger from dying cells (damage-associated molecular patterns, DAMPs). These signals contribute to the mobilization and maturation of antigen-presenting cells (dendritic cells) and the subsequent activation of a specific response. The immune system enters into a fight with the surviving malignant cells, which allows achieving long-term remission or even complete recovery of the patient.
By the staff of the Institute of Biology and Biomedicine of N.I. Lobachevsky National Research University and Ghent University (Belgium) under the guidance of Prof. Dmitry Krysko is conducting research on the possibility of activating immunogenic cell death during photodynamic antitumor therapy (PDT). PDT is included in the list of minimally invasive and low-toxic methods of treating several types of cancer, during which specific agents (photosensitizers) are injected into the body, accumulating in the tumor and forming toxic compounds under the influence of visible light irradiation, thereby causing its death.
In the recently published article Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death (A new photodynamic anti-cancer therapy based on porphyrazines causes immunogenic cell death) in the highly rated international journal Scientific Reports (Nature Research group, journal impact factor 4.576; ranked 7th in the top world journals exceeding 350,000 citations for According to the Journal Citation Reports), scientists experimentally tested new variants of photosensitizers for the effectiveness of fibrosarcoma cell death under photodynamic exposure.
New variants of photosensitizers from the porphyrazine group were synthesized by the staff of the Razuvaev Institute of Organometallic Chemistry of the Russian Academy of Sciences (Ph.D. Klapshina L.G., Ph.D. Lermontov S.A.).
"The article describes the chemical and physical properties of photodynamic agents, their accumulation rate and localization features in tumor cells, as well as describes the main ways of cell death during photodynamic exposure using these photosensitizers," says one of the authors of the study, Director of the Institute of Biology and Biomedicine of UNN, Professor Maria Vedunova.
In addition, it has been shown that PDT releases DAMPs based on the studied compounds, which contribute to the attraction and maturation of dendritic cells. Animal studies have shown that injection of PDT-exposed tumor cells into mice as a vaccine promotes the development of a persistent adaptive immune response, thanks to which the growth of an experimental tumor was significantly slowed down in such animals.
The revealed abilities of new compounds to actively engage the immune system in the fight against tumor cells open up new opportunities in overcoming the resistance of tumors to therapy, and, consequently, contribute to improving the effectiveness of treatment and the quality of life of patients.
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