The morbidity of extrahepatic cholangiocarcinoma (CCA) has increased markedly in the past few decades. However, most patients with extrahepatic CCA are diagnosed at an advanced stage and thus cannot receive curative resection in time. To increase the long-term survival probability of nonresectable extrahepatic CCA patients, it is highly desirable to develop alternative treatment strategies. Photodynamic therapy is a highly efficient method for the ablation of cancer cells, but the conventional photosensitizers (PSs) suffer from self-quenching after local accumulation in organelles. To tackle this challenge, we herein develop a mitochondria-anchoring photosensitizer, TTVPHE, with aggregation-induced emission (AIE) characteristics for efficient ablation of extrahepatic CCA cells through the mitochondrial injury pathway. The TTVPHE probe shows significant advantages in terms of fast cell penetration ability, selective mitochondria-targeting ability, and excellent ROS generation ability under white light irradiation. Moreover, the probe can in situ monitor the mitochondrial injury process by translocation from mitochondria to the nuclear membrane. The ultrastructural changes in the morphology of mitochondria under PDT were also characterized using high resolution TEM. This AIE-active probe is promising for the treatment of advanced stage CCA.

中文翻译：

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线粒体锚定和AIE活性光敏剂用于自我监测的胆管癌治疗

在过去的几十年中，肝外胆管癌（CCA）的发病率显着增加。但是，大多数肝外CCA患者被诊断为晚期，因此不能及时接受根治性切除。为了增加不可切除的肝外CCA患者的长期生存可能性，非常需要开发替代治疗策略。光动力疗法是消融癌细胞的高效方法，但是传统的光敏剂（PSs）在细胞器中局部积累后会遭受自猝灭作用。为了解决这一挑战，我们在这里开发了一种固定线粒体的光敏剂TTVPHE具有聚集诱导发射（AIE）特性，可通过线粒体损伤途径有效消融肝外CCA细胞。所述TTVPHE在快速细胞渗透能力而言，探针显示显著优点，选择性线粒体靶向能力，并且在白光下照射优良ROS产生的能力。此外，该探针可以通过从线粒体到核膜的移位来原位监测线粒体的损​​伤过程。还使用高分辨率TEM表征了PDT下线粒体形态的超微结构变化。这种AIE活性探针有望用于晚期CCA的治疗。