Enhanced photosensitizing properties of protein bound curcumin
Enhanced photosensitizing properties of protein bound curcumin
复制标题
DOI：
10.1016/j.lfs.2019.116710
复制
发表时间：
2019-09-15
期刊：
影响因子：
6.1
通讯作者：
Viappiani, Cristiano
中科院分区：
文献类型：
--
作者：
Cozzolino, Marco;Delcanale, Pietro;Viappiani, Cristiano
目的：天然化合物姜黄素已被提出用于许多药理应用。尽管这种分子具有很好的化疗特性，但姜黄素的使用在很大程度上受到其在水中化学不稳定性的限制。在这项工作中，我们建议使用水溶性蛋白来克服这一问题，并将其应用于光动力治疗肿瘤。材料与方法：将姜黄素与牛血清白蛋白结合，采用MTT法和共聚焦成像技术研究姜黄素的光物理性质及其对细胞活力的影响。主要发现：牛血清白蛋白以中等亲和力结合姜黄素，并溶解疏水化合物，保持其光物理性质数小时。细胞活力分析表明，当姜黄素与血清白蛋白结合时，它是一种有效的HeLa细胞光敏剂，其性能优于单独姜黄素。共聚焦荧光成像显示，当姜黄素单独递送时，它优先与线粒体结合，而与牛血清白蛋白结合的姜黄素在细胞内的其他位置被发现，这一事实可能与在这种情况下观察到的更高的光毒性有关。意义：光敏化合物姜黄素与血清白蛋白结合后具有较高的生物利用度，可用于提高药物在肿瘤光动力治疗中的效率。
Aims: The naturally occurring compound curcumin has been proposed for a number of pharmacological applications. In spite of the promising chemotherapeutic properties of the molecule, the use of curcumin has been largely limited by its chemical instability in water. In this work, we propose the use of water soluble proteins to overcome this issue in perspective applications to photodynamic therapy of tumors.Materials and methods: Curcumin was bound to bovine serum albumin and its photophysical properties was studied as well as its effect on cell viability after light exposure through MTT assay and confocal imaging.Key findings: Bovine serum albumin binds curcumin with moderate affinity and solubilizes the hydrophobic compound preserving its photophysical properties for several hours. Cell viability assays demonstrate that when bound to serum albumin, curcumin is an effective photosensitizer for HeLa cells, with better performance than curcumin alone. Confocal fluorescence imaging reveals that when curcumin is delivered alone, it preferentially associates with mitochondria, whereas curcumin bound to bovine serum albumin is found in additional locations within the cell, a fact that may be related to the higher phototoxicity observed in this case.Significance: The higher bioavailability of the photosensitizing compound curcumin when bound to serum albumin may be exploited to increase the efficiency of the drug in photodynamic therapy of tumors.