State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Changchun 130012, China.
Key Lab for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130012, China.
Anal Chem. 2020 Apr 21;92(8):6081-6087. doi: 10.1021/acs.analchem.0c00497. Epub 2020 Apr 2.
Mitochondrion is one of the most important organelles and becomes a target in many cancer therapeutic strategies. Mitochondrial microenvironments in response to therapeutic methods are the key to understand therapeutic mechanisms. However, they are almost rarely studied. Herein, the mitochondrial microenvironments, including mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) after different photodynamic therapy (PDT) dosages, were monitored by fluorescent imaging and compared among three cell lines (HepG2, MCF-7, and LO2). Furthermore, the fluctuations of intramitochondrial pHs were revealed via a plasmonic mitochondrion-targeting surface-enhanced Raman scattering (SERS) pH nanosensor. Results indicate that the MMP decreases gradually with the ROS generation and the cancerous cells exhibit less response to excess ROS relative to normal cells. On the other hand, the pH value in the mitochondria decreases initially and then increases when the amount of ROS increases. The LO2 cell is preliminarily evidenced to have a higher self-adjustment ability due to its better tolerance to differential intra/extracellular pHs. This study may provide a basis for an in-depth understanding of the mechanisms of the mitochondrial targeting-based PDT therapeutic processes. It is also helpful for more accurate and useful diagnosis according to intramitochondrial microenvironments and improvement on therapy efficiency of cancers.
线粒体是最重要的细胞器之一，也是许多癌症治疗策略的靶点。线粒体对治疗方法的微环境是理解治疗机制的关键，但它们几乎很少被研究。本文通过荧光成像监测了不同光动力治疗（PDT）剂量后的线粒体膜电位（MMP）和活性氧（ROS）等线粒体微环境，并在三种细胞系（HepG2、MCF-7 和 LO2）中进行了比较。此外，通过等离子体线粒体靶向表面增强拉曼散射（SERS）pH 纳米传感器揭示了线粒体内部 pH 值的波动。结果表明，MMP 随 ROS 的产生而逐渐降低，并且与正常细胞相比，癌细胞对过量 ROS 的反应较少。另一方面，当 ROS 增加时，线粒体中的 pH 值先降低后升高。由于 LO2 细胞对细胞内外 pH 值的差异具有更好的耐受性，初步证明其具有更高的自我调节能力。本研究可为深入了解基于线粒体靶向的 PDT 治疗过程的机制提供依据，也有助于根据线粒体内部微环境进行更准确、更有用的诊断，并提高癌症的治疗效率。
