An NIR‐Fluorophore‐Based Therapeutic Endoplasmic Reticulum Stress Inducer. Issue 33 (1st July 2018)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Advanced materials. Volume 30:Issue 33(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-07-01
• Subjects: ER stress -- mitochondrial complexes I -- NDUFS1 -- NIR fluorphores; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.201800475
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: 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. Abstract : A therapeutic endoplasmic reticulum (ER) stress inducer based on an NIR heptamethine fluorophore is developed. The fluorophore targets the mitochondrial complex I protein NDUFS1 to provide sufficient specificity and imaging guidance for cancer cell death. This work may present a novel strategy to develop molecular target‐specific theranostic agent by targeting mitochondrial protein.