CC BY
12B-O-16
BIOMEDICAL PHOTONICS
Comparison of the antitumor activity of the photosensitizer based on indotricarbocyanine dye and Photolon
M.P. Samtsov, D.S. Tarasov, A.P. Lugovski
A.N Sevchenko Institute for Applied Physical Problems of BSU, 220045 Minsk, Belarus
tarasovds@bsu.by
Photodynamic therapy (PDT) takes place one of the leading positions among modern methods of treating malignant neoplasms. Further development of the PDT method is associated with the creation of a new generation of photosen-sitizers (PS), the requirements for which are not limited only by a high therapeutic effect. The scientific community is developing new PSs that are activated by light in the transparency window of biological tissues (700-900 nm). This makes it possible to increase the depth of both damage and diagnosis of neoplasms.
Based on the results of complex studies of the photophysical properties of a number of indotricarbocyanine dyes in model media and tumor models on experimental animals in vivo, a dye with optimal properties for theranostics of malignant neoplasms was selected [1]. At the current stage of development, a synthesis scheme and laboratory procedures for obtaining a new PS have been worked out, a prototype of the drug dosage form based on glucose has been developed, and optimal conditions for a photodynamic therapy session in experiments with transplantable tumors on laboratory animals have been determined. This paper presents the results of a comparison of its therapeutic properties with PS Photolon (RUE Belmedpreparaty, Belarus) approved for use in clinical practice.
The study of the antitumor activity of photosensitizers was carried out on sexually mature inbred female mice of the C57BL/6 line, which were inoculated with Ehrlich ascites carcinoma on the outer surface of the thigh. Studies for both photosensitizers were performed 10 days after tumor inoculation into animals in one experiment. Experimental and control groups were formed from animals with tumors, the volume of which reached 30-40 mm3 (the linear dimensions of the tumor node were about 4-6 mm).
For both PS, the dose of the drug, the start time of photoexposure, the wavelength of radiation, the energy and power density of irradiation were selected in accordance with the protocol for its use. At the same time, the PDT parameters were identical in terms of the following points: the same tumor model, the method of drug administration, the parameters of the light spot on the surface of the tumor node.
To activate the indotricarbocyanine photosensitizer during PDT, a semiconductor laser light source with a generation wavelength of 750 nm (IAPP, Belarus) was used. PDT with the photosensitizer Photolon was carried out using a therapeutic apparatus "PDT-laser" (B. I. Stepanov Institute of Physics, Belarus) with a laser generation wavelength of 660
The antitumor activity of photosensitizers was evaluated according to the recommendations of the Pharmaceutical Committee for preclinical studies of drugs [2]. Within 21 days, the condition of the animals and the dynamics of tumor growth in the experimental and control groups were monitored. For both studied PSs, the same dynamics of tumor growth after PDT was observed. After PDT in animals of the test groups [PDT with PS Photolon] and [PDT with in-dotricarbocyanine PS], burns with the formation of a scab were observed at the site of tumor localization on days 3-5. On days 14 and 21 after PDT, no tumors were detected in any of the test groups. In the control groups, tumor growth continued, on the 21st day the tumor volume increased by 6-8 times.
Thus, under optimal conditions for photodynamic therapy, PS Photolon and the new PS demonstrate the same antitumor activity for the Ehrlich ascites carcinoma.
[1] A.A. Lugovski, M.P. Samtsov, K.N. Kaplevsky, D.S. Tarasau, E.S. Voropay, P.T. Petrov, Y.P. Istomin, Novel indotricarbocyanine dyes covalently bonded to polyethylene glycol for theranostics, Journal of Photochemistry and Photobiology A: Chemistry, vol. 316, pp. 31-36, (2016).
[2] A.N. Mironova (red.) Rukovodstvo po provedeniyu doklinicheskih issledovanij lekarstvennyh sredstv. CHast' pervaya. (M.: Grif
i K), Glava 40, (2012).
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