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<p>Carbon monoxide (CO) has recently been well-established as a promising therapeutic modality against cancer. The development of transition-metal-free and tumor-targeted delivery platforms for CO is highly demanded but remains very sporadic. Herein, we developed a polyprodrug system for the co-delivery of CO and a chemotherapeutic agent combretastin A-4 (CA-4) to the tumor site based on a chemiexcitation mechanism. Such a poly-prodrug successfully achieved the co-activation of CO and CA-4 in response to H<sub>2</sub>O<sub>2</sub> at the tumor site both <i>in vitro</i> and <i>in vivo</i>. Importantly, a synergist effect between CO and CA-4 was observed in suppressing tumor growth in a mouse tumor model. It is anticipated that such a poly-prodrug system could be potentially adapted for the co-delivery of CO and another drug payload for combinational therapy for other indications.</p>

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Self-assembled carbon monoxide nanoprodrug for chemiexcitation-triggered synergistic chemotherapy against breast cancer

  • 期刊论文

  • 发表日期：

    2025年1月8日

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  • Shunfei Cui,
  • Yiyao Pan,
  • Chenzhe Ma,
  • Bin Qi,
  • Qingqiang Min,
  • Ming Li,
  • Huabing Chen,
  • Hengte Ke,
  • Xingyue Ji

摘要

Carbon monoxide (CO) has recently been well-established as a promising therapeutic modality against cancer. The development of transition-metal-free and tumor-targeted delivery platforms for CO is highly demanded but remains very sporadic. Herein, we developed a polyprodrug system for the co-delivery of CO and a chemotherapeutic agent combretastin A-4 (CA-4) to the tumor site based on a chemiexcitation mechanism. Such a poly-prodrug successfully achieved the co-activation of CO and CA-4 in response to H2O2 at the tumor site both in vitro and in vivo. Importantly, a synergist effect between CO and CA-4 was observed in suppressing tumor growth in a mouse tumor model. It is anticipated that such a poly-prodrug system could be potentially adapted for the co-delivery of CO and another drug payload for combinational therapy for other indications.