Wang Kewei, Xiao Xuan, Jiang Maolin, Li Jisi, Zhou Jielian, Yuan Youyong
School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 511442, P. R. China.
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, P. R. China.
Small. 2021 Sep;17(36):e2102610. doi: 10.1002/smll.202102610. Epub 2021 Jul 29.
Pyroptosis is an inflammatory form of programmed cell death that can effectively eliminate malignant cells and boost anticancer immunity. However, most of the current pyroptosis inducers lack cell selectivity, which may cause severe side effects for cancer therapy. In this work, for the first time, the authors discovered that the commonly used near-infrared (NIR) fluorogenic hemicyanine (CyNH ) induces pyrolysis to kill cancer cells and boost antitumor immunity. Cancer cells overexpressing the NAD(P)H: quinone oxidoreductase isozyme 1 (NQO1)-responsive theranostic (NCyNH ) are designed for selective cell pyroptosis and are nonfluorescent with low toxicity before activation. In the presence of NQO1, the fluorescence of CyNH is restored and can selectively initiate pyroptosis of cancer cells and further lead to systemic antitumor immunity activation for solid tumor therapy. Thus, this fluorogenic NIR dye may represent a novel theranostic agent for the selective initiation of tumor pyroptosis.
细胞焦亡是一种程序性细胞死亡的炎症形式，能够有效清除恶性细胞并增强抗癌免疫力。然而，目前大多数细胞焦亡诱导剂缺乏细胞选择性，这可能会给癌症治疗带来严重的副作用。在这项研究中，作者首次发现常用的近红外（NIR）荧光半菁（CyNH）可诱导细胞焦亡以杀死癌细胞并增强抗肿瘤免疫力。设计了过表达烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）：醌氧化还原酶同工酶1（NQO1）响应性诊疗试剂（NCyNH）的癌细胞用于选择性细胞焦亡，并且在激活前无荧光且毒性低。在NQO1存在的情况下，CyNH的荧光得以恢复，并可选择性地引发癌细胞的焦亡，进而导致全身抗肿瘤免疫激活以用于实体瘤治疗。因此，这种荧光近红外染料可能代表一种用于选择性引发肿瘤焦亡的新型诊疗试剂。
