Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Via J.H. Dunant 3, 21100 Varese, Italy.
Faculty of Sciences, Byrom Street Campus, Liverpool John Moores University, Liverpool L3 3AF, UK.
Int J Mol Sci. 2024 Mar 10;25(6):3187. doi: 10.3390/ijms25063187.
Photodynamic therapy (PDT) relies on the combined action of a photosensitizer (PS), light at an appropriate wavelength, and oxygen, to produce reactive oxygen species (ROS) that lead to cell death. However, this therapeutic modality presents some limitations, such as the poor water solubility of PSs and their limited selectivity. To overcome these problems, research has exploited nanoparticles (NPs). This project aimed to synthesize a PS, belonging to the BODIPY family, covalently link it to two NPs that differ in their lipophilic character, and then evaluate their photodynamic activity on SKOV3 and MCF7 tumor cell lines. Physicochemical analyses demonstrated that both NPs are suitable for PDT, as they are resistant to photobleaching and have good singlet oxygen (O) production. In vitro biological analyses showed that BODIPY has greater photodynamic activity in the free form than its NP-bounded counterpart, probably due to greater cellular uptake. To evaluate the main mechanisms involved in PDT-induced cell death, flow cytometric analyses were performed and showed that free BODIPY mainly induced necrosis, while once bound to NP, it seemed to prefer apoptosis. A scratch wound healing test indicated that all compounds partially inhibited cellular migration of SKOV3 cells.
光动力疗法(PDT)依赖于光敏剂(PS)、适当波长的光和氧气的联合作用,产生导致细胞死亡的活性氧(ROS)。然而,这种治疗方式存在一些局限性,例如 PS 的水溶性差和选择性有限。为了克服这些问题,研究人员利用了纳米颗粒(NPs)。本项目旨在合成一种属于 BODIPY 家族的 PS,将其共价连接到两种亲脂性不同的 NPs 上,然后评估其对 SKOV3 和 MCF7 肿瘤细胞系的光动力活性。物理化学分析表明,两种 NPs 都适合 PDT,因为它们耐光漂白且具有良好的单线态氧(O)产生能力。体外生物学分析表明,BODIPY 在游离形式下比其 NP 结合形式具有更高的光动力活性,这可能是由于细胞摄取增加所致。为了评估 PDT 诱导细胞死亡的主要机制,进行了流式细胞术分析,结果表明游离 BODIPY 主要诱导坏死,而一旦与 NP 结合,似乎更倾向于凋亡。划痕愈合试验表明,所有化合物都部分抑制了 SKOV3 细胞的迁移。