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阳离子磷树枝状聚合物增强孟加拉玫瑰红对基底细胞癌细胞系的光动力活性。

Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

作者信息

Dabrzalska Monika, Janaszewska Anna, Zablocka Maria, Mignani Serge, Majoral Jean Pierre, Klajnert-Maculewicz Barbara

机构信息

Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz , Pomorska 141/143, 90-236 Lodz, Poland.

Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences , Sienkiewicza 112, 90-363 Lodz, Poland.

出版信息

Mol Pharm. 2017 May 1;14(5):1821-1830. doi: 10.1021/acs.molpharmaceut.7b00108. Epub 2017 Apr 6.

Abstract

In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

摘要

在过去几十年中,光动力疗法成为治疗基底细胞癌的一种有用工具。然而,由于光敏剂的不良特性,如溶解性差或缺乏选择性,它仍然存在局限性。树枝状大分子是在生物医学领域广泛研究的聚合物,可能作为光敏剂载体发挥作用,并提高光动力治疗的效果。在此,我们描述了阳离子磷树枝状大分子与孟加拉玫瑰红的静电复合物在单线态氧产生、细胞摄取以及对三种基底细胞癌细胞系的光毒性等方面的评估。将摩尔比为5:1的孟加拉玫瑰红 - 阳离子树枝状大分子复合物与游离孟加拉玫瑰红进行了比较。所得结果表明,复合物在水性介质中的单线态氧产生明显高于游离孟加拉玫瑰红。与游离光敏剂相比,复合物的细胞摄取高出2至7倍。重要的是,孟加拉玫瑰红、孟加拉玫瑰红 - 树枝状大分子复合物以及树枝状大分子本身对所有三种细胞系均无暗毒性。此外,我们观察到复合物的光毒性显著增强,可能是由于细胞摄取量高。基于所得结果,我们得出结论,孟加拉玫瑰红 - 阳离子树枝状大分子复合物在基底细胞癌的光动力治疗中具有潜力。

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