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

Jong Jin Kim, Yong An Lee, Dongdong Su, Jungyeol Lee, Sung Jin Park, Beomsue Kim, Jia Hui Jane Lee, Xiao Liu, Seong Soon Kim, Myung Ae Bae, Jun Seok Lee, Seong Cheol Hong, Lu Wang, Animesh Samanta, Haw Young Kwon, So Young Choi, Jun Young Kim, Young Hyun Yu, Hyung Ho Ha, Zhenxun WangWai Leong Tam, Bing Lim, Nam Young Kang, Young Tae Chang

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)14673-14686
Number of pages14
JournalJournal of the American Chemical Society
Volume141
Issue number37
DOIs
Publication statusPublished - 2019 Sep 18
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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