Scholarlink

<p>Despite the promise of ferroptosis in cancer therapy, its insufficient potency and off-target toxicity remain significant challenges. Few studies have explored the therapeutic potential of nanoparticle (NP)-mediated active targeting strategies to induce robust ferroptosis in colon cancer (COC) cells effectively. In this study, we developed sialic acid (SA)-targeted NPs by conjugating artesunate (ART) with alanine (Ala) and phenylboronic acid (PBA) to formulate ART-Ala-PBA NPs (AAP NPs). Compared with nontargeted ART-Ala NPs, AAP NPs accumulated significantly within cancer tissues, inhibited tumor growth, and improved the survival rates of mice with COC, while exhibiting minimal toxicity. Mechanistically, AAP NPs induce ferroptosis through the accumulation of reactive oxygen species and the downregulation of the SLC7A11-GPX4 axis. Deep data-independent acquisition (DIA) proteomics revealed a novel suppression of ribonucleotide reductase regulatory subunit M1 (RRM1), which synergizes with canonical ferroptosis pathways to amplify lipid peroxidation. RNA sequencing further indicated that AAP NPs uniquely modulate autophagy-related processes, suggesting a multimodal mechanism distinct from the alterations in amino acid metabolism induced by parental ART formulations. Collectively, AAP NPs represent the first carrier-free nanoassembly leveraging PBA-mediated SA targeting to co-activate ferroptosis via dual ROS/GPX4-RRM1 regulation, offering a translatable paradigm for precision nanotherapy of COC.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Self-assembled phenylboronic acid nanomedicine targets sialic acid to synergistically activate ferroptosis via RRM1 suppression and GPX4 Inhibition for precision colon cancer therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月25日

查看全文
  • Dake Song,
  • Jianing Li,
  • Yidan Zhu,
  • Qijun Hui,
  • Hengkai Qi,
  • Hanrui Yu,
  • Lin Chen,
  • Yue Qian,
  • Yuanyuan Guo,
  • Minjie Wei,
  • Qiutong Guan,
  • Zhenhua Li

摘要

Despite the promise of ferroptosis in cancer therapy, its insufficient potency and off-target toxicity remain significant challenges. Few studies have explored the therapeutic potential of nanoparticle (NP)-mediated active targeting strategies to induce robust ferroptosis in colon cancer (COC) cells effectively. In this study, we developed sialic acid (SA)-targeted NPs by conjugating artesunate (ART) with alanine (Ala) and phenylboronic acid (PBA) to formulate ART-Ala-PBA NPs (AAP NPs). Compared with nontargeted ART-Ala NPs, AAP NPs accumulated significantly within cancer tissues, inhibited tumor growth, and improved the survival rates of mice with COC, while exhibiting minimal toxicity. Mechanistically, AAP NPs induce ferroptosis through the accumulation of reactive oxygen species and the downregulation of the SLC7A11-GPX4 axis. Deep data-independent acquisition (DIA) proteomics revealed a novel suppression of ribonucleotide reductase regulatory subunit M1 (RRM1), which synergizes with canonical ferroptosis pathways to amplify lipid peroxidation. RNA sequencing further indicated that AAP NPs uniquely modulate autophagy-related processes, suggesting a multimodal mechanism distinct from the alterations in amino acid metabolism induced by parental ART formulations. Collectively, AAP NPs represent the first carrier-free nanoassembly leveraging PBA-mediated SA targeting to co-activate ferroptosis via dual ROS/GPX4-RRM1 regulation, offering a translatable paradigm for precision nanotherapy of COC.

Graphical abstract