Polyelectrolyte Microcapsules as a Tool to Enhance Photosensitizing Effect of Chlorin E6

Ekaterina P. Brodovskaya; Larisa А. Tararina; Mikhail N. Zharkov; Irina A. Khutorskaya; Denis E. Yakobson; Amina Al-khadj Aioub; Igor V. Maev; Andrey V. Zaborovskiy; Dina V. Yunina; Sergei V. Tsaregorodtsev; Gleb  B. Sukhorukov; Nikolay A. Pyataev

doi:10.18413/rrpharmacology.9.10055

Authors

Ekaterina P. Brodovskaya Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University https://orcid.org/0000-0002-1060-9843
Larisa А. Tararina Federal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation https://orcid.org/0000-0001-8006-698X
Mikhail N. Zharkov Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University https://orcid.org/0000-0002-8272-1973
Irina A. Khutorskaya Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University. https://orcid.org/0000-0001-5553-0525
Denis E. Yakobson Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University https://orcid.org/0000-0002-7675-0823
Amina Al-khadj Aioub Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University https://orcid.org/0000-0002-2793-6760
Igor V. Maev Federal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation https://orcid.org/0000-0001-6114-564X
Andrey V. Zaborovskiy Federal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation https://orcid.org/0000-0002-7923-9916
Dina V. Yunina Federal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation https://orcid.org/0000-0001-8901-9557
Sergei V. Tsaregorodtsev ederal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation https://orcid.org/0000-0002-0254-0516
Gleb B. Sukhorukov Skolkovo Institute of Science and Technology https://orcid.org/0000-0001-6213-0562
Nikolay A. Pyataev Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University. https://orcid.org/0000-0002-9688-7640

DOI:

https://doi.org/10.18413/rrpharmacology.9.10055

Abstract

Introduction: Photodynamic therapy is a promising method of tumors treatment using photosensitizers and light of a certain wavelength. PS modification improves and enhances the phototoxic effect with decreased dark cytotoxicity.

Materials and Methods: We compared the photosensitizing effect of polyelectrolyte microcapsules with chlorin E6 (ClE6) and free ClE6 at equivalent concentrations on murine fibroblast culture L929 using in vitro tests. Microcapsules were prepared layer by layer, sequentially depositing oppositely charged polyelectrolytes onto spherical CaCO₃ particles. Cellular uptake of capsules was assessed using confocal microscopy. MTT test was used for a study of cell viability, and the relative amount of ROS was determined by the fluorescent method.

Results: Microcapsules with ClE6 (in all tested concentrations) after exposure to red light (660 nm) reduced cell viability from 20% to 5%, while these capsules did not have dark cytotoxicity. Free ClE6 at the same concentrations as in the capsules after irradiation reduced viability from 65% to 35%. The level of ROS in the group of cells with capsules was 2 times higher compared to the group with CLE6.

Discussion: The most probable mechanism of toxicity increase is creation of a higher ROS concentration and effect localization in the area of microcapsule interaction with the cell membrane. ROS production activation may stem from capsules providing a higher local PS concentration in the cell or nearby than the drug’s free form.

Conclusion: The inclusion of chlorin E6 in polymer capsules reduced dark toxicity and increased the photosensitizing effect compared to the free form of ClE6.

Graphical Abstract

Keywords:

polyelectrolyte microcapsules, photodynamic therapy, chlorin E6, phototoxicity, ROS – reactive oxygen species

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Author Contribution

Ekaterina P. Brodovskaya, Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University

Candidate of Medical Sciences, Associate Professor of the Department of Anesthesiology and Resuscitation with courses in Valeology, Life Safety and Disaster Medicine of the Medical Institute, National Research Ogarev Mordovia State University; e-mail: kitten-777@mail.ru; ORCID ID https://orcid.org/0000-0002-1060-9843. Drawing up a research plan and general guidance, designing the experiment, conducting the experiment, analyzing literary data, and writing the text of the article.

Larisa А. Tararina , Federal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation

Senior Lecturer, Department of Pharmacology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry; e-mail: 79104906528@yandex.ru; ORCID ID https://orcid.org/0000-0001-8006-698X. Development of the experiment design, conducting the experiment, analysis of literary data, and writing the text of the article.

Mikhail N. Zharkov , Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University

Head of Pharmacokinetics and Targeted Pharmacotherapy Laboratories, National Research Ogarev Mordovia State University; e-mail: ykbsn@mail.ru; ORCID ID https://orcid.org/0000-0002-8272-1973. Conducting the experiment, analysis of clinical manifestations, and statistical analysis of the data.

Irina A. Khutorskaya , Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University.

Candidate of Biological Sciences, Engineer of Pharmacokinetics and Targeted Pharmacotherapy Laboratories, National Research Ogarev Mordovia State University; e-mail: alfa200890@yandex.ru; ORCID ID https://orcid.org/0000-0001-5553-0525. Conducting the experiment, analysis of clinical manifestations, and statistical analysis of the data.

Denis E. Yakobson , Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University

Engineer of Pharmacokinetics and Targeted Pharmacotherapy Laboratories, National Research Ogarev Mordovia State University; e-mail: ykbsn@mail.ru; ORCID ID https://orcid.org/0000-0002-7675-0823. Conducting the experiment, analysis of clinical manifestations, and statistical analysis of the data.

Amina Al-khadj Aioub , Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University

Engineer of Pharmacokinetics and Targeted Pharmacotherapy Laboratories, National Research Ogarev Mordovia State University; e-mail: amina.aioub1@gmail.com; ORCID ID https://orcid.org/0000-0002-2793-6760. Conducting the experiment, analysis of clinical manifestations, and statistical analysis of the data.

Igor V. Maev, Federal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation

Dr. Habil. Med, Full Professor, Member of the Russian Academy of Sciences, Head of the Department of Propaedeutics of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry; e-mail: igormaev@rambler.ru; ORCID ID https://orcid.org/0000-0001-6114-564X. Drawing up a research plan and general guidance, designing and conducting the experiment, analyzing literary data, and writing the text of the article.

Andrey V. Zaborovskiy , Federal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation

Dr. Habil. Med., Associate Professor, Head of the Department of Pharmacology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry; e-mail: azabor@mail.ru; ORCID ID https://orcid.org/0000-0002-7923-9916. Developing the experiment design, analyzing literary data. and writing the text of the article.

Dina V. Yunina, Federal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation

Lecturer, Department of Pharmacology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry; e-mail: yunina@msmsu.ru; ORCID ID https://orcid.org/0000-0001-8901-9557. Developing the experiment design, analyzing literary data writing the text of the article.

Sergei V. Tsaregorodtsev, ederal State Budgetary Educational Institution of Higher Education "A.I. Yevdokimov Moscow State University of Medicine and Dentistry" of the Ministry of Healthcare of the Russian Federation

Lecturer, Department of Pharmacology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry; e-mail: sergiotsar@yandex.ru; ORCID ID https://orcid.org/0000-0002-0254-0516. Developing the experiment design, analyzing literary data, and writing the text of the article.

Gleb B. Sukhorukov , Skolkovo Institute of Science and Technology

Dr. Habil. Med., Full Professor, Vladimir Zelman Center for Neurobiology and Brain Rehabilitation, Skolkovo Institute of Science and Technology, Russia; Professor, School of Engineering and Materials Science, Queen Mary University of London, e-mail: g.sukhorukov@skoltech.ru; ORCID ID https://orcid.org/0000-0001-6213-0562. Developing the experiment design, conducting the experiment, analyzing literary data, and writing the text of the article.

Nikolay A. Pyataev , Federal State Budgetary Educational Institution of Higher Education, National Research Ogarev Mordovia State University.

Dr. Habil. Med., Associate Professor, Head of the Department of Anesthesiology and Resuscitation with courses in Valeology, Life Safety and Disaster Medicine, National Research Ogarev Mordovia State University; e-mail: pyataevna@mail.ru; ORCID ID https://orcid.org/0000-0002-9688-7640. Drawing up a research plan and general guidance, developing the design of the experiment, analyzing literary data, and writing the text of the article.