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

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

  • J Am Chem Soc. 2019 Sep 18;141(37):14673-14686. doi: 10.1021/jacs.9b06068.
Jong-Jin Kim 1 2,  Yong-An Lee 1 3,  Dongdong Su 1,  Jungyeol Lee 4,  Sung-Jin Park 1,  Beomsue Kim 1,  Jia Hui Jane Lee 3 5,  Xiao Liu 2,  Seong Soon Kim 6,  Myung Ae Bae 6,  Jun-Seok Lee 7,  Seong Cheol Hong 7,  Lu Wang 1 8,  Animesh Samanta 1 9,  Haw-Young Kwon 2,  So-Young Choi,  Jun-Young Kim 10,  Young Hyun Yu 11,  Hyung-Ho Ha 11,  Zhenxun Wang 3,  Wai Leong Tam 3 12 13,  Bing Lim 3 14,  Nam-Young Kang 1 4,  Young-Tae Chang 1 2
Affiliations

Affiliations

  • 1 Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Agency for Science , Technology and Research (A*STAR) , Singapore 138667 , Singapore.
  • 2 Center for Self-assembly and Complexity , Institute for Basic Science (IBS) , Pohang 37673 , Republic of Korea.
  • 3 Genome Institute of Singapore, Agency for Science , Technology and Research (A*STAR) , 60 Biopolis Street , Singapore 138672 , Singapore.
  • 4 New Drug Discovery Center , DGMIF , Daegu 41061 , Republic of Korea.
  • 5 School of Biological Sciences , Nanyang Technological University , Singapore 637551 , Singapore.
  • 6 Bio & Drug Discovery Division , Korea Research Institute of Chemical Technology , Yuseong-Gu , Gajeong-ro 141 , Daejeon 34114 , Republic of Korea.
  • 7 Molecular Recognition Research Center , Korea Institute of Science and Technology , 5, Hwarang-ro 14-gil , Seoul 02792 , Republic of Korea.
  • 8 Department of Chemical Biology , Max Planck Institute for Medical Research , Heidelberg 69120 , Germany.
  • 9 Chemical Sciences and Technology Division , CSIR - National Institute for Interdisciplinary Sciences and Technology (CSIR - NIIST) , Industrial Estate P O , Pappanamcode , Thiruvananthapuram 695019 , India.
  • 10 A-fourth, SL VAXiGEN , KOREA BIO PARK , Daewangpangyo-ro 700, Bundang-gu , Seongnam-si , Gyenggi-do 13488 , Korea.
  • 11 Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences 11 , Sunchon National University , Suncheon 57922 , Republic of Korea.
  • 12 Cancer Science Institute of Singapore , National University of Singapore , Singapore 117599 , Singapore.
  • 13 Department of Biochemistry, Yong Loo Lin School of Medicine , National University of Singapore , Singapore 117597 , Singapore.
  • 14 Merck Sharp and Dohme Translational Medicine Research Centre , 8A Biomedical Grove , Singapore 138648 , Singapore.
PMID: 31436967 DOI: 10.1021/jacs.9b06068
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.

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