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A mitochondria-targeted and viscosity-sensitive near-infrared fluorescent probe for visualization of fatty liver, inflammation and photodynamic cancer therapy
Chemical Engineering Journal ( IF 15.1 ) Pub Date : 2022-06-23 , DOI: 10.1016/j.cej.2022.137762
Li Fan , Qi Zan , Xiaodong Wang , Xue Yu , Shuohang Wang , Yuewei Zhang , Qianqian Yang , Wenjing Lu , Shaomin Shuang , Chuan Dong

Elucidating the intrinsic relationship between disease and mitochondrial viscosity is great significance for understanding the diagnosis and treatment of fatty liver, inflammation and cancer. However, the development of a single mitochondrial viscosity fluorescent probe capable of visualizing multiple disease models and achieving photodynamic cancer therapy function is severely deficient and remains a great challenge. Herein we intelligently designed a mitochondria-targeted and viscosity-sensitive near-infrared (NIR) fluorescent probe POTA-OH, containing a p-hydroxydiphenylamino substituted oxanthracene moiety as the strong electron donor (D), a pyridinium cationic unit as the electron acceptor (A) and the mitochondria-targeted group. With increasing the viscosity level, POTA-OH displayed a significant “turn-on” fluorescence behavior at 720 nm, and an excellent linear relationship with viscosity from 0.89 cP to 945 cP. Meanwhile, POTA-OH could achieve effective reactive oxygen species production upon a 635 nm red laser irradiation. Using POTA-OH, we have demonstrated the visualization of fatty liver tissues, inflammation living mice, tumor living mice and even clinic cancer patient tissues samples via mitochondrial viscosity imaging. Furthermore, we revealed that POTA-OH has the potential of simultaneous PDT treatment in vitro and immediate evaluation of its therapeutic effect. Importantly, high-efficient PDT of POTA-OH has also successfully achieved for in vivo PDT antitumor, making it a promising integrated reagent for cancer diagnosis, treatment and even evaluation of PDT efficacy.



中文翻译:

一种线粒体靶向和粘度敏感的近红外荧光探针,用于脂肪肝、炎症和光动力癌症治疗的可视化

阐明疾病与线粒体粘度之间的内在关系对于理解脂肪肝、炎症和癌症的诊断和治疗具有重要意义。然而,能够可视化多种疾病模型并实现光动力癌症治疗功能的单个线粒体粘度荧光探针的开发严重不足,仍然是一个巨大的挑战。在这里,我们智能地设计了一种线粒体靶向和粘度敏感的近红外 (NIR) 荧光探针 POTA-OH,包含p-羟基二苯氨基取代的氧蒽部分作为强电子供体(D),吡啶鎓阳离子单元作为电子受体(A)和线粒体靶向基团。随着粘度水平的增加,POTA-OH 在 720 nm 处显示出显着的“开启”荧光行为,并且在 0.89 cP 至 945 cP 范围内与粘度具有良好的线性关系。同时,在 635 nm 红色激光照射下,POTA-OH 可以实现有效的活性氧生成。使用 POTA-OH,我们已经通过线粒体粘度成像展示了脂肪肝组织、炎症活小鼠、肿瘤活小鼠甚至临床癌症患者组织样本的可视化。此外,我们发现 POTA-OH在体外具有同时进行 PDT 治疗的潜力并立即评估其治疗效果。重要的是,POTA-OH的高效PDT也成功实现了体内PDT抗肿瘤,使其成为一种很有前景的癌症诊断、治疗甚至PDT疗效评估的综合试剂。

更新日期:2022-06-23
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