研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

光敏剂金属化对芳基铼组装体在前列腺癌的影响。

The Effect of Photosensitizer Metalation Incorporated into Arene-Ruthenium Assemblies on Prostate Cancer.

发表日期:2023 Sep 02
作者: Lucie Paulus, Manuel Gallardo-Villagrán, Claire Carrion, Catherine Ouk, Frédérique Martin, Bruno Therrien, David Yannick Léger, Bertrand Liagre
来源: Cell Death & Disease

摘要:

前列腺癌是男性中第二常见的癌症,是一个重大的健康问题。尽管有各种治疗方法,但还是观察到许多副作用。光动力疗法是一种非侵入性方法,它使用光敏物质和光线通过分子内产生活性氧物质来诱导细胞死亡,几乎没有副作用。然而,光动力疗法中使用的一些光敏物质在生物介质中的溶解度极低,因此需要进行功能化或载体化来确保内化。为此,我们使用了芳烃-钌笼来将光敏物质传递给癌细胞。这些金属-组装体可以将光敏物质嵌入笼体内部或通过光敏物质构建组装体。在本研究中,我们想确定这些光敏物质中心添加金属(镁,钴,锌)是否起作用。我们的结果显示绝大多数化合物对DU 145和PC-3人类前列腺癌细胞具有细胞毒效应。通过荧光定位,证实了这些组装体在细胞质内的内化。对细胞凋亡过程的分析显示,存在剪切前半胱天冬蛋白酶-3和聚腺苷二磷酸核糖聚合酶的现象,从而导致DNA断裂的强烈诱导。最后,光敏物质中存在金属会降低光动力疗法的效果,甚至可能完全消除其效果。
Prostate cancer is the second most common cancer for men and a major health issue. Despite treatments, a lot of side effects are observed. Photodynamic therapy is a non-invasive method that uses photosensitizers and light to induce cell death through the intramolecular generation of reactive oxygen species, having almost no side effects. However, some of the PSs used in PDT show inherent low solubility in biological media, and accordingly, functionalization or vectorization is needed to ensure internalization. To this end, we have used arene-ruthenium cages in order to deliver PSs to cancer cells. These metalla-assemblies can host PSs inside their cavity or be constructed with PS building blocks. In this study, we wanted to determine if the addition of metals (Mg, Co, Zn) in the center of these PSs plays a role. Our results show that most of the compounds induce cytotoxic effects on DU 145 and PC-3 human prostate cancer cells. Localization by fluorescence confirms the internalization of the assemblies in the cytoplasm. An analysis of apoptotic processes shows a cleavage of pro-caspase-3 and poly-ADP-ribose polymerase, thus leading to a strong induction of DNA fragmentation. Finally, the presence of metals in the PS decreases PDT's effect and can even annihilate it.