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Theranostics 2023; 13(4):1370-1380. doi:10.7150/thno.79282 This issue Cite

Research Paper

Theranostics application of tumor-initiating cell probe TiY in non-small cell lung cancer

Yong-An Lee^1✉, Chee Chong Jonathan Lek^1,2, Gao Rong¹, Zhengwei Wu^1,3, S Shathishwaran¹, Jia Hui Jane Lee^1,2, Wai Leong Tam^1,2,3,4, Torsten Wuestefeld^1,2,5, Sung-Jin Park⁶, Sangyong Jung⁷, Beomsue Kim⁸, Nam-Young Kang^9✉, Young-Tae Chang^10,11✉

1. Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, 138672, Singapore.
2. School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore.
3. Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
4. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
5. National Cancer Centre Singapore, 169610, Singapore.
6. Institute of Bioengineering and Bioimaging (IBB), Agency for Science, Technology and Research (A*STAR), Singapore, 138667, Singapore.
7. Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.
8. Neural Circuit Research Group, Korea Brain Research Institute (KBRI) Daegu, 41068, Republic of Korea.
9. Department of Convergence IT Engineering, Pohang University of Science and Technology, Pohang, 37673, Republic of Korea.
10. Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang, 37673, Republic of Korea.
11. Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.

✉ Corresponding author: Young-Tae Chang. Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea. E-mail: ytchangac.kr.

Abstract

Background: Tumor-initiating cells (TIC) often elude conventional cancer treatment, which results in metastasis and cancer relapse. Recently, studies have begun to focus on the TIC population in tumors to provide better therapeutic options. Previously, we have reported the successful development of a TIC-specific probe TiY with the binding target as vimentin. While a low concentration of TiY showed a TIC visualization, at a high concentration, TiY induced selective toxicity onto TIC in vitro. In this study, we aim to assess TiY's applicability in theranostics purposes, from in vivo visualization to therapeutic effect toward TIC, in cancer mouse models.

Methods: We performed cell experiments with the TIC line model derived from resected primary non-small cell lung cancer (NSCLC) patient tumor. The animal model studies were conducted in mice of NSCLC patient-derived xenograft (PDX). TiY was intravenously delivered into the mice models at different concentrations to assess its in vivo TIC-selective staining and therapeutic effect.

Results: We demonstrated the TIC-selective identification and therapeutic effect of TiY in animal models. TiY treatment induced a significant ablation of the TIC population in the tumor, and further molecular study elucidated that the mechanism of TiY is through vimentin dynamics in TIC.

Conclusion: The results underscore the applicability of TiY for cancer treatment by selectively targeting soluble vimentin in TIC.

Keywords: Tumor-initiating cells, Non-small cell lung cancer, Fluorescent probe, cancer treatment

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