背景：肿瘤启动细胞（TIC）经常逃避传统的癌症治疗，导致转移和癌症复发。最近，一些研究开始关注肿瘤中的TIC群体，以提供更好的治疗选择。我们先前报道了一种定位于微丝蛋白的TIC特异性探针TiY的成功开发。低浓度的TiY显示了TIC可视化，而高浓度的TiY在体外引发了对TIC的选择性毒性。本研究旨在评估TiY在治疗和诊断方面的适用性，从体内可视化到对恶性肿瘤小鼠模型中TIC的治疗效果。 方法：我们在原发性非小细胞肺癌（NSCLC）患者肿瘤中提取的肿瘤细胞系模型中进行了细胞实验。动物模型研究在NSCLC患者皮移种（PDX）的小鼠中进行。TiY以不同浓度静脉注射入小鼠模型，以评估其在体内TIC选择性染色和治疗效果。 结果：我们证明了TiY在动物模型中的TIC选择性鉴定和治疗效果。TiY治疗引发了肿瘤中TIC人口的显著消融，并进一步的分子研究阐明了TiY的机制是通过微丝蛋白动力学来实现对TIC的作用。 结论：这些结果强调了通过选择性靶向TIC可溶性微丝蛋白来治疗癌症的可行性。 ©作者

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.© The author(s).