An NIR-Fluorophore-Based Therapeutic Endoplasmic Reticulum Stress Inducer

作者：Wang, Yang; Luo, Shenglin; Zhang, Chi; Liao, Xingyun; Liu, Tao; Jiang, Zhongyong; Liu, Dengqun; Tan, Xu; Long, Lei; Wang, Yu; Chen, Zelin; Liu, Yunsheng; Yang, Fan; Gan, Yibo; Shi, Chunmeng^*

来源：Advanced Materials, 2018, 30(33): 1800475.

DOI：10.1002/adma.201800475

• ER stress
• mitochondrial complexes I
• NDUFS1
• NIR fluorphores

The endoplasmic reticulum (ER) stress signaling or unfolded protein response (UPR) is a common feature of many human diseases, including cancer. Excessive activation of ER stress directly induces cell death, holding a new promising strategy for the therapeutic intervention of cancer. Current ER-stress-inducing agents mainly target UPR components or proteasomes, which exert limited treatment efficacy and undesired side effects due to unselective ER stress and poor tumor-specific distribution. In this study, a unique near-infrared (NIR) fluorophore, IR-34, is synthesized and identified to selectively and efficiently trigger tumoricidal ER stress by targeting the mitochondrial protein NDUFS1. IR-34 is demonstrated to specifically accumulate in living cancer cells for tumor NIR imaging and drastically inhibit tumor growth and recurrence without causing apparent toxicity. Thus, this multifunctional NIR fluorophore may represent a novel theranostic agent for tumor imaging-guided treatment and also strengthens the idea that mitochondria could be a useful target for therapeutic ER stress in cancer cells.

• 出版日期2018-8-16
• 单位创伤、烧伤与复合伤研究国家重点实验室