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<p>In the clinical management of lung cancer, conventional therapeutic agents still face huge challenges such as poor target specificity, low tumor enrichment, and sub-optimal treatment outcomes. Therefore, it is of great significance to develop an advanced theranostic system with superior tumor-targeting specificity and excellent theranostic capability for the precise diagnosis and treatment of lung cancer. Herein, a tumor-targeted, ferrocene-bearing, and covalently immobilizable probe dIR-CDF is rationally reported for near infrared imaging-guided photodynamic-ferroptosis synergistic therapy of non-small cell lung cancer (NSCLC). Its potential for sensitive imaging and effective therapy of NSCLC is systematically investigated both <i>in vitro</i> and <i>in vivo.</i> Taking advantage of the feature of highly over-expressed sulfenated proteins in the tumor microenvironment, dIR-CDF can specifically target integrin αvβ<sub>3</sub>-positive NSCLC and is covalently anchored within the tumors through the specific reaction between 1,3-cyclohexanedione and sulfenic acid, which significantly enhances the accumulation and retention of dIR-CDF in tumors. More notably, the sustained release of ferrocene induces serious cell ferroptosis and synergizes with photodynamic effect under 808 nm irradiation, achieving efficient suppression of NSCLC tumor in living mice. This work offers a powerful and universal theranostic system for the effective treatment of NSCLC.</p>

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A covalent tumor-targeted theranostic system for NIR imaging-guided photodynamic-ferroptosis synergistic therapy of lung cancer

  • 期刊论文

  • 发表日期：

    2026年7月8日

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  • Yurong Fan,
  • Hongyuan Wen,
  • Zhitao Zhu,
  • Chaoxiang Cui,
  • Yuqi Zhang,
  • Zhongsheng Zhao,
  • Miao Li,
  • Yiming Feng,
  • Mei Hu,
  • Xingxiang Ren,
  • Zhengzhong Lv,
  • Zhixin Han,
  • Haibin Shi,
  • Guohua Fan

摘要

In the clinical management of lung cancer, conventional therapeutic agents still face huge challenges such as poor target specificity, low tumor enrichment, and sub-optimal treatment outcomes. Therefore, it is of great significance to develop an advanced theranostic system with superior tumor-targeting specificity and excellent theranostic capability for the precise diagnosis and treatment of lung cancer. Herein, a tumor-targeted, ferrocene-bearing, and covalently immobilizable probe dIR-CDF is rationally reported for near infrared imaging-guided photodynamic-ferroptosis synergistic therapy of non-small cell lung cancer (NSCLC). Its potential for sensitive imaging and effective therapy of NSCLC is systematically investigated both in vitro and in vivo. Taking advantage of the feature of highly over-expressed sulfenated proteins in the tumor microenvironment, dIR-CDF can specifically target integrin αvβ3-positive NSCLC and is covalently anchored within the tumors through the specific reaction between 1,3-cyclohexanedione and sulfenic acid, which significantly enhances the accumulation and retention of dIR-CDF in tumors. More notably, the sustained release of ferrocene induces serious cell ferroptosis and synergizes with photodynamic effect under 808 nm irradiation, achieving efficient suppression of NSCLC tumor in living mice. This work offers a powerful and universal theranostic system for the effective treatment of NSCLC.