# KP-06-Russia/9/11.12.2020
„Efficacy and antitumor mechanisms of photodynamic therapy using photosensitizers based on bacteriochlorins with different molecular charges“

Funded by NSF-MES-Bulgaria and RFBR-Russian Federation

   

Partners:

Institute of Electronics, Bulgarian Academy of Sciences

I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

   

   

   

   

    Bulgarian scientific team

Ekaterina Borisova, Assoc. prof., PhD, IE-BAS – team coordinator

Ivan Angelov, Assoc. prof., PhD, IE-BAS – team co-coordinator

Alexander Gisbrecht, Assoc. prof., PhD, IE-BAS

Vanya Mantareva, Assoc. Prof., PhD, IOChCP-BAS

Vesselin Kussovski, Assoc.Prof., PhD, IMicroB-BAS

Biliana Nikolova, Assoc. prof. PhD, IBPhBME-BAS

Ivan Iliev, Assoc. Prof., PhD, IEMPAM-BAS

Biliana Georgieva, Assist. Prof., PhD, IOMT-BAS

Boriana Yakimova, Assistant, PhD student, IOChCP-BAS

Deyan Ivanov,PhD student, IE-BAS

Lidia Zaharieva, Physicist - IE-BAS, Master's student "Medical Physics",Phys. Dept. - SU

   

    Russian scientific team

Evgenija Kogan, , Professor, DSci in Medicine, Head of the Department of Anatomic Pathology, I.M. Sechenov First Moscow State Medical University – team coordinator

Gennady Meerovich, PhD, senior researcher, Prokhorov General Physics Institute of Russian Academy of Sciences

Elena Makarova, PhD, Federal State Unitary Enterprise “State Scientific Centre “Organic Intermediates & Dyes Institute”

Sergey Gonchukov, Professor, National Research Nuclear University MEPhI

Saida Karshieva, PhD, senior researcher, N.N. Blokhin National Cancer Research Center of Oncology

Ekaterina Akhluystina, PhD student, National Research Nuclear University MEPhI

The participants in the project are the Institute of Electronics of the Bulgarian Academy of Sciences, Bulgaria and the First Moscow State Medical University I.M. Sechenov, Moscow, Russia. The partners have prepared a project proposal for the programme COMPETITION FOR FINANCIAL SUPPORT FOR BILATERAL PROJECTS – BULGARIA – RUSSIA 2019 – 2020 for cooperation in the field of investigations into efficacy and mechanisms of impact in photodynamic therapy with photosensitizers on the basis of bacteriochlorins with different molecular charges on cancerous neoplasia, as well as on the treatment of pathogenic bacteria and viruses. The Bulgarian team includes specialists in the field of physics, chemistry and biology working in the long-term cooperation in the field of photodynamic medicine, with complementary knowledge and skills for the needs of the successful implementation of such an interdisciplinary project.
The actuality and relevance of the project is based on the need to expand the possibilities of using photodynamic therapy (PDT) in relation to tumor neoplasms, as well as in the treatment of viral and bacterial infections, both by increasing the effectiveness of the impact on the specific object and due to the reduction of the side effects of photodynamic treatment. The latter can be achieved by increasing the selectivity of the photodynamic action and reducing the residual phototoxicity by accelerating the elimination of photosensitizers (PS) from healthy tissues adjacent to the treated object (e.g., tumor) including the skin and blood of the patient. One of the ways to solve this problem is an PDT using PS with effective excitation in the spectral range (710-800 nm) within the "therapeutic window" of biological tissues. In line with current research in the field of PDTs, one of the most promising sensitizers in this range are the derivatives of synthetic bacteriochlorines, characterized by increased rate of excretion from the body, high quantum yield of singlet oxygen, as well as simpler procedures for their synthesis and wide availability of raw materials.
The proposed project is mainly devoted to the physical investigation of the physicochemical, pharmacokinetic and photo-physical properties of PS - new synthesized electroneutral and polycationic derivatives of synthetic bacteriochlorins, capable of providing an effective photodynamic effect in the treatment of deeper-situated tumors. Particular attention will be paid to the relationship between the photodynamic properties of the newly synthesized PSs with the magnitude of the charge of their molecules. The scientific novelty of the study is that new PSs, based on bacteriochlorins, will be created and studied, with properties optimized to increase the efficiency of PDT, including through the charge of molecules. The synthesis strategy will include the creation of new PSs with optimal chemical structure and charge of the molecules, as well as adherence to proven practice methods for their solely and / or co-administration with other therapeutic drugs in tumor treatment procedures.

PLANNED STUDIES

It is planned for a first time to investigate the in-vitro phenomena that occur when the treated cells interact with the newly-synthetized PSs with different molecular charges. The mechanisms of interaction and destruction of cell fragments during sensitization and photodynamic treatment will be studied and analyzed.
For a first time, in vitro levels and kinetics of accumulation and localization of the generated FSs with different molecular charges in the target cells will be investigated. At the same time, it is planned to evaluate the binding of new PS to immune cells involved in innate immune responses (macrophages, monocytes, neutrophils) and with the vascular endothelial cells. The scientific significance of the results of this type of studies is that new knowledge will be gained about the effects of photosensitizers based on electroneutral and polycationic derivatives of synthetic bacteriochlorins in eukaryotic cells, both from tumor and healthy tissues.
The processes of sensitization and the efficacy of photodynamic therapy of tumors of experimental animals using bacteriochlorine PS with different charges will also be investigated to determine the pharmacokinetics, bio-distribution and elimination rate of pS from healthy tissues.

Chemical structure of porphyrin-like photosensitizers.

   

   

EXPECTED RESULTS

These studies will clarify the role of the charge of photosensitizer molecules in terms of antitumor efficacy and mechanisms of tumor tissue destruction. As a result, we expect to clarify new requirements regarding the optimal composition and structure of the investigated PS in the specific PDT procedures applied.
The project envisages the investigation of the mechanisms and efficacy of photodynamic action on tumors of laboratory animals using the optimal from the point of view of efficiency synthesized PS, based on the results obtained in the frames of in vitro cell line studies. This will allow us to develop optimal PDT approaches for tumors with different genesis. The results of this strategy will be applicable in future technological developments with respect to preclinical and clinical trials of prospective PSs.
The results of the project will enable an establishment of basic protocols for the strategy for photodynamic treatment in oncology, and its implementation will significantly contribute to the solving a wide range of problems in the treatment of tumors and clarifying the prospects for applications of photodynamic inactivation in pathogens microorganisms and viruses.

   

   

   

   

Presentations under project # KP-06-Russia/9/11.12.2020 „Efficacy and antitumor mechanisms of photodynamic therapy using photosensitizers based on bacteriochlorins with different molecular charges”:

22 January2021, Online project kick-off meeting E. Borisova, Efficacy and antitumor mechanisms of photodynamic therapy using bacteriochlorins – project overview LINK

   

   

Publications under # KP-06-Russia/9/11.12.2020 „Efficacy and antitumor mechanisms of photodynamic therapy using photosensitizers based on bacteriochlorins with different molecular charges”:

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