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A Near-Infrared Probe Tracks and Treats Lung Tumor Initiating Cells by Targeting HMOX2.

Jong-Jin KimYong-An LeeDongdong SuJungyeol LeeSung-Jin ParkBeomsue KimJia Hui Jane LeeXiao LiuSeong Soon KimMyung Ae BaeJun-Seok LeeSeong Cheol HongLu WangAnimesh SamantaHaw-Young KwonSo-Young ChoiJun-Young KimYoung Hyun YuHyung-Ho HaZhenxun WangWai Leong TamBing LimNam-Young KangYoung Tae Chang
Published in: Journal of the American Chemical Society (2019)
Tumor initiating cells (TIC) are resistant to conventional anticancer therapy and associated with metastasis and relapse in cancer. Although various TIC markers and their antibodies have been proposed, it is limited to the use of antibodies for in vivo imaging or treatment of TIC. In this study, we discovered heme oxygenase 2 (HMOX2) as a novel biomarker for TIC and developed a selective small molecule probe TiNIR (tumor initiating cell probe with near infrared). TiNIR detects and enriches the functionally active TIC in human lung tumors, and through the photoacoustic property, TiNIR also visualizes lung TIC in the patient-derived xenograft (PDX) model. Furthermore, we demonstrate that TiNIR inhibits tumor growth by blocking the function of HMOX2, resulting in significantly increased survival rates of the cancer model mice. The novel therapeutic target HMOX2 and its fluorescent ligand TiNIR will open a new path for the molecular level of lung TIC diagnosis and treatment.
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