Tumor initiating cells (TIC) are resistant to conventional anti-cancer therapy and associated with metastasis and relapse in cancer. Although various TIC markers and their antibodies have been proposed, it is limited to 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 Infra-Red). TiNIR detects and enriches the functionally active TIC in human lung tumors, and through photoacoustic proper-ty, 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 molecular level of lung TIC diagnosis and treatment.

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