State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Changchun 130012, People's Republic of China.
Institute of Frontier Medical Science, Jilin University, Changchun 130021, People's Republic of China.
Analyst. 2019 Sep 21;144(18):5521-5527. doi: 10.1039/c9an01231a. Epub 2019 Aug 9.
Subcellular mitochondrion has become a target for improving the therapeutic efficiency and reducing side damage to normal cells via a combination of many therapeutic strategies. However, the underlying molecular mechanisms associated with cell death induced by subcellular dysfunction remain unknown or disputed. In this study, we investigated the dynamic molecular changes of living mitochondria upon phototherapy (photothermal therapy plus photodynamic therapy, PTT & PDT) by surface-enhanced Raman scattering spectroscopy (SERS) and intended to disclose the photo-induced cell death route in breast cancer cells (MCF-7) taking into account the mitochondrion. Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved clinic blood-injection near-infrared angiographic contrast agent and a PTT & PDT drug, was used for the evaluation of the phototherapy effect. The results revealed that the content of phenylalanine (Phe) in mitochondria evidently increased during the phototherapy-induced cell death process. Moreover, the phototherapy-induced cell apoptosis was mainly regulated through the DNA structures. We expect that the understanding of mitochondrial molecular stress responses will be helpful for the diagnosis and therapy of cellular processes associated with mitochondria and provide valuable guidance for the further design and development of more effective therapeutic platforms and methods at the sub-cellular level.
亚细胞线粒体已成为通过多种治疗策略相结合来提高治疗效率和减少对正常细胞的副作用的目标。然而，与亚细胞功能障碍引起的细胞死亡相关的潜在分子机制尚不清楚或存在争议。在这项研究中，我们通过表面增强拉曼散射光谱（SERS）研究了光疗（光热疗法加光动力疗法，PTT 和 PDT）对活线粒体的动态分子变化，并考虑到线粒体，旨在揭示乳腺癌细胞（MCF-7）中的光诱导细胞死亡途径。吲哚菁绿（ICG）是美国食品和药物管理局（FDA）批准的临床血液注射近红外血管造影对比剂和 PTT 和 PDT 药物，用于评估光疗效果。结果表明，在光疗诱导的细胞死亡过程中，线粒体中苯丙氨酸（Phe）的含量明显增加。此外，光疗诱导的细胞凋亡主要通过 DNA 结构进行调节。我们期望对线粒体分子应激反应的理解将有助于与线粒体相关的细胞过程的诊断和治疗，并为进一步设计和开发更有效的治疗平台和方法提供有价值的指导，以达到亚细胞水平。
