Efficacy of photodynamic therapy in an experimental mice tuberculosis model

The objective: to study the efficacy of antimicrobial photodynamic therapy (APDT) using hydroxyaluminum phthalocyanine (Photosens) as a photosensitizer in the experimental model of tuberculosis infection in mice.

Subjects and Methods. Balb/cmice were infected with the multiple drug resistant (MDR) strain of M. tuberculosis Beijing BO/W148. APDT with hydroxyaluminum phthalocyanine and red laser light exposure were started on Day 45. A total of 4 sessions of APDT on the projection of both lungs, liver and spleen were performed. On Day 60, the therapeutic eff ect of APDT

was assessed by evaluation of severity of mycobacterial load and specific granulomatous infiltration in the lungs, liver and spleen. The absorption of light energy of laser radiation by the chest and abdominal walls, as well as tissues of lungs, liver and spleen was determined by photometry using afluovisor.

Results. The tissues of the experimental animal retain a significant amount of light energy, however, the residual value of light transmission is sufficient to provide a pronounced therapeutic effect which manifests itself as a significant decrease of mycobacterial load and specific inflammatory process in all the studied internal organs.

Conclusion. APDT may be an effective tool to treat some forms of tuberculous infection including those caused by M. tuberculosis with MDR.

1. Bredikhin D.A., Nikonov S.D., Cherednichenko A.G., Korbut A.I., Petrenko T.I. In vitro photodynamic inactivation of Mycobacterium tuberculosis by methylene blue. Tuberculosis and Lung Diseases, 2019, vol. 97, no. 7, pp. 28–33. (In Russ.)

2. Bredikhin D.A., Nikonov S.D., Cherednichenko A.G., Petrenko T.I. In vitro photodynamic inactivation of Mycobacterium tuberculosis by radachlorin. Tuberculosis and Lung Diseases, 2018, vol. 96, no. 3, pp. 5–10. (In Russ.)

3. Vasilyeva I.A., Belilovsky E.M., Borisov S.E., Sterlikov S.A. Multiple drug resistant tuberculosis in the world and Russian Federation. Tuberculosis and Lung Diseases, 2017, vol. 95, no. 11, pp. 5–17. (In Russ.)

4. The Russian Ministry of Health. Tuberkulez u vzroslykh. Klinicheskie rekomendatsii. [Tuberculosis in adults: Guidelines]. 2020. Available: https://cr.minzdrav.gov.ru/schema/16_1/ Accessed August 30, 2023

5. Nikonov S.D., Bredikhin D.A., Belogorodtsev S.N., Shvarts Ya.Sh. Photodynamic inactivation of Mycobacterium tuberculosis by aluminum phthalocyanine. Byulleten Eksperimentalnoy Biologii i Meditsiny, 2023, no. 3, pp. 350-354. (In Russ.)

6. Nikonov S.D., Smolentsev M.N., Krasnov D.V., Bredikhin D.A., Belogorodtsev S.N. Photodynamic therapy in tuberculous pleural empyema. Tuberculosis and Lung Diseases, 2021, vol. 99, no. 5, pp. 51–56. (In Russ.)

7. Semenov D.Yu., Vasiliev Yu.L., Dydykin S.S., Stranadko E.F., Shubin V.K., Bogomazov Yu.K., Morokhotov V.A., Scherbyuk A.N., Morozov S.V., Zakharov Yu.I. Antimicrobial and antimycotic photodynamic therapy (review). BiomedicalPhotonics, 2021, vol. 10, no. 1, pp. 25-31. (In Russ.)

8. Castano, A.P.; Demidova, T.N.; Hamblin, M.R. Mechanisms in photodynamic therapy: part one – photosensitizers, photochemistry and cellular localization. Photodiagnosis Photodyn. Ther., 2004, no. 1, pp. 279–293.

9. Falk-Mahapatra R., Gollnick S.O. Photodynamic Therapy and Immunity: An Update, Photochem. Photobiol, 2020, vol. 96, no. 3, pp. 550–559.

10. Global tuberculosis report 2021, Geneva, World Health Organization 2021. Available at: https://www.who.int/publications/i/item/9789240037021 Accessed Aug 30, 2023.

11. Guterres K.B., Rossi G.G., Menezes L.B., Anraku de Campos M.M., Iglesias B.A. Preliminary evaluation of the positively and negatively charge effects of tetra-substituted porphyrins on photoinactivation of rapidly growing mycobacteri. Tuberculosis (Edinb.), 2019, vol. 117, pp. 45–51.

12. Jeong B., Kim J.K., Bae T., Park I. Effect of photodynamic therapy enhanced by methylene blue on drug-resistant Mycobacterium smegmatis. J. Bacteriol. Virol., 2020, vol. 50, no. 4, pp. 235–24.

13. Lukyanets E.A. Phthalocyanines as photosensitizers in the photodynamic therapy of cancer. Journal of Porphyrins and Phthalocyanines, 1999, vol. 3, no. 6, pp. 424–432.

14. Rossi G.G., Guterres K.B., Hahn da Silveira C., Schneider Moreira K., Lima Burgo T.A., Almeida Iglesias B., Anraku de Campos M.M. Peripheral tetra-cationic Pt(II) porphyrins photo-inactivating rapidly growing mycobacteria: First application in mycobacteriology. Microbial Pathogenesis, 2020, vol. 148, pp. 104455.

15. Shim I., Choi M., Min Y., Seok K.H., Kim J.K., Jeong J.Y., Oak C.H., Park I. Effect of methylene blue-mediated photodynamic therapy on wild-type and ciprofloxacin-resistant Mycobacterium smegmatis. J. Bacteriol. Virol., 2016, vol. 46, pp. 27–35.

16. Shleeva M., Savitsky A., Kaprelyants A. Photoinactivation of mycobacteria to combat infection diseases: current state and perspectives. Appl. Microbiol. Biotechnol., 2021, vol. 105, no. 10, pp. 4099–4109.