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

Q3 Pharmacology, Toxicology and Pharmaceutics
E. P. Brodovskaya, L. A. Tararina, Mikhail N. Zharkov, Irina A. Khutorskaya, D. E. Yakobson, A. Al-khadj Aioub, I. Maev, A. V. Zaborovskiy, D. V. Yunina, S. V. Tsaregorodtsev, G. Sukhorukov, N. Pyataev
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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.
将聚电解质微胶囊作为增强氯素 E6 光敏效应的工具
引言光动力疗法是一种利用光敏剂和特定波长的光治疗肿瘤的有效方法。PS 改性可改善和增强光毒性效应,降低暗细胞毒性。材料与方法:我们通过体外试验比较了含有氯素 E6(ClE6)的聚电解质微胶囊和等浓度的游离 ClE6 对小鼠成纤维细胞 L929 培养物的光敏作用。微胶囊是一层一层制备的,依次将带相反电荷的聚电解质沉积在球形 CaCO3 颗粒上。使用共聚焦显微镜评估细胞对胶囊的吸收情况。MTT 试验用于研究细胞活力,荧光法测定 ROS 的相对含量。结果含有 ClE6(所有测试浓度)的微胶囊暴露于红光(660 纳米)后,细胞存活率从 20% 降至 5%,而这些胶囊没有暗细胞毒性。与胶囊中相同浓度的游离 ClE6 在照射后可使细胞存活率从 65% 降至 35%。与含有 CLE6 的细胞组相比,含有胶囊的细胞组中的 ROS 水平高出 2 倍。讨论:毒性增加的最可能机制是在微胶囊与细胞膜相互作用的区域产生更高的 ROS 浓度和效应定位。激活 ROS 的产生可能是由于胶囊在细胞内或附近提供了比游离态药物更高的局部 PS 浓度。结论与游离态的 ClE6 相比,在聚合物胶囊中加入氯素 E6 可降低暗毒性并提高光敏效果。
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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