Mitochondria-anchoring and AIE-Active Photosensitizer for Self-Monitored Cholangiocarcinoma Therapy
Mitochondria-anchoring and AIE-Active Photosensitizer for Self-Monitored Cholangiocarcinoma Therapy
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用于自我监测胆管癌治疗的线粒体锚定和 AIE 活性光敏剂
DOI：
10.1039/d0qm00503g
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发表时间：
2020
影响因子：
7
通讯作者：
Min Li
中科院分区：
文献类型：
--
作者：
Tao Zhou;Jianfang Zhu;Dan Shang;Chuxing Chai;Youzhen Li;Haiying Sun;Yongqin Li;Meng Gao;Min Li
在过去的几十年里，肝外胆管细胞癌(CCA)的发病率显著上升。然而，肝外CCA的诊断大多处于晚期，不能及时根治性切除。为了提高不能切除的肝外CCA患者的长期生存概率，开发替代治疗策略是非常必要的。光动力疗法是一种高效的肿瘤细胞消融方法，但传统的光敏剂(PSS)在细胞器内局部积聚后会发生自猝灭。为了应对这一挑战，我们在此开发了一种线粒体锚定光敏剂TTVPhe，具有聚集诱导发射(AIE)特性，可通过线粒体损伤途径有效地消融肝外CCA细胞。TTVPhe探针在白光照射下表现出快速的细胞穿透能力、选择性的线粒体靶向能力和良好的ROS产生能力等显著优势。此外，该探针还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。用高分辨透射电子显微镜观察了光动力作用下线粒体形态的超微结构变化。该AIE活性探针有望用于晚期CCA的治疗。
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.