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Azulitox—A Pseudomonas aeruginosa P28-Derived Cancer-Cell-Specific Protein Photosensitizer
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-11-03 , DOI: 10.1021/acs.biomac.0c01216 Heinz Fabian Raber 1 , Thomas Heerde 1 , Suzanne Nour El Din 1 , Carolin Flaig 1, 2 , Fabienne Hilgers 3 , Nora Bitzenhofer 3 , Karl-Erich Jäger 3, 4 , Thomas Drepper 3 , Kay-Eberhard Gottschalk 2 , Nicholas Emil Bodenberger 5 , Tanja Weil 5 , Dennis Horst Kubiczek 1 , Frank Rosenau 1, 5
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-11-03 , DOI: 10.1021/acs.biomac.0c01216 Heinz Fabian Raber 1 , Thomas Heerde 1 , Suzanne Nour El Din 1 , Carolin Flaig 1, 2 , Fabienne Hilgers 3 , Nora Bitzenhofer 3 , Karl-Erich Jäger 3, 4 , Thomas Drepper 3 , Kay-Eberhard Gottschalk 2 , Nicholas Emil Bodenberger 5 , Tanja Weil 5 , Dennis Horst Kubiczek 1 , Frank Rosenau 1, 5
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Azulitox as a new fusion polypeptide with cancer cell specificity and phototoxicity was generated and is composed of a photosensitizer domain and the cell-penetrating peptide P28. The photosensitizer domain (EcFbFP) was derived from a bacterial blue-light receptor, which belongs to the family of light-oxygen-voltage proteins and produces reactive oxygen species (ROS) upon excitation. P28 is derived from the cupredoxin protein azurin that is known to specifically penetrate cancer cells and bind to the tumor suppressor protein p53. We show that the P28 domain specifically directs and translocates the fused photosensitizer into cancer cells. Under blue-light illumination, Azulitox significantly induced cytotoxicity. Compared to the extracellular application of EcFbFP, Azulitox caused death to about 90% of cells, as monitored by flow cytometry, which also directly correlated with the amount of ROS produced in the cells. Azulitox may open new avenues toward targeted polypeptide–photosensitizer-based photodynamic therapies with reduced systemic toxicity compared to conventional photosensitizers.
中文翻译：
Azulitox-铜绿假单胞菌P28衍生的癌细胞特异性蛋白光敏剂
产生了具有癌细胞特异性和光毒性的新型融合多肽Azulitox，其由光敏剂结构域和细胞穿透肽P28组成。光敏剂域（EcFbFP）来源于细菌蓝光受体，该细菌属于光氧电压蛋白家族，在激发时会产生活性氧（ROS）。P28衍生自铜氧还蛋白蛋白天青素，已知其特异性地穿透癌细胞并与肿瘤抑制蛋白p53结合。我们显示P28域专门指导和转移融合的光敏剂到癌细胞中。在蓝光下，Azulitox显着诱导细胞毒性。通过流式细胞仪监测，与EcFbFP的细胞外应用相比，Azulitox导致约90％的细胞死亡，这也与细胞中产生的ROS量直接相关。与传统的光敏剂相比，Azulitox可能会为靶向多肽-基于光敏剂的光动力疗法开辟新途径，从而降低全身毒性。
更新日期：2020-12-14
中文翻译：
Azulitox-铜绿假单胞菌P28衍生的癌细胞特异性蛋白光敏剂
产生了具有癌细胞特异性和光毒性的新型融合多肽Azulitox，其由光敏剂结构域和细胞穿透肽P28组成。光敏剂域（EcFbFP）来源于细菌蓝光受体，该细菌属于光氧电压蛋白家族，在激发时会产生活性氧（ROS）。P28衍生自铜氧还蛋白蛋白天青素，已知其特异性地穿透癌细胞并与肿瘤抑制蛋白p53结合。我们显示P28域专门指导和转移融合的光敏剂到癌细胞中。在蓝光下，Azulitox显着诱导细胞毒性。通过流式细胞仪监测，与EcFbFP的细胞外应用相比，Azulitox导致约90％的细胞死亡，这也与细胞中产生的ROS量直接相关。与传统的光敏剂相比，Azulitox可能会为靶向多肽-基于光敏剂的光动力疗法开辟新途径，从而降低全身毒性。
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