Scholarlink

<p>The prevalence of immunosuppressive, tumor-associated macrophages (TAM) in the tumor microenvironment of hepatocellular carcinoma (HCC) compromises the efficacy of sorafenib (SF)-based, ferroptosis-inducing systemic therapies. Increasing the susceptibility of tumor cells and TAMs to ferroptosis represents a promising breakthrough in improving the therapeutic outcomes of SF. Here, we show that the upregulation of ferroptosis suppressor protein 1 (FSP1) counteracts SF-induced ferroptosis independently of glutathione peroxidase 4 (GPX4) and correlates with increased immunosuppressive TAM infiltration and unfavorable prognosis. In preclinical HCC mouse models, biomimetic nanoparticles, co-loaded with SF and the FSP1 inhibitor viFSP1 and designed to simultaneously target tumor cells and immunosuppressive TAMs, enhance ferroptosis in both cell types, promoting antigen presentation and cytotoxic T cell infiltration. Furthermore, combinatorial treatment with an anti-PD-L1 antibody suppresses metastasis and tumor recurrence. Thus, our nanoparticle-based dual-target strategy induces synergistic ferroptosis-immunotherapy in HCC, and represents a promising strategy to sensitize tumors to SF treatment, driving the remodeling of the immunosuppressive tumor microenvironment.</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

Co-delivery of sorafenib and an FSP1 inhibitor triggers dual ferroptosis in tumor cells and immunosuppressive macrophages for enhanced immunotherapy in mouse models of hepatocellular carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月18日

查看全文
  • Chuanyu Tang,
  • Cheng He,
  • Decheng Wang,
  • Jie Guo,
  • Xiangyi Yin,
  • Hanjie Ye,
  • Lei Wu,
  • Yuling Zhang,
  • Silue Zeng,
  • Xiaojun Zeng,
  • Chengbo Liu,
  • Jingqin Chen,
  • Chihua Fang

摘要

The prevalence of immunosuppressive, tumor-associated macrophages (TAM) in the tumor microenvironment of hepatocellular carcinoma (HCC) compromises the efficacy of sorafenib (SF)-based, ferroptosis-inducing systemic therapies. Increasing the susceptibility of tumor cells and TAMs to ferroptosis represents a promising breakthrough in improving the therapeutic outcomes of SF. Here, we show that the upregulation of ferroptosis suppressor protein 1 (FSP1) counteracts SF-induced ferroptosis independently of glutathione peroxidase 4 (GPX4) and correlates with increased immunosuppressive TAM infiltration and unfavorable prognosis. In preclinical HCC mouse models, biomimetic nanoparticles, co-loaded with SF and the FSP1 inhibitor viFSP1 and designed to simultaneously target tumor cells and immunosuppressive TAMs, enhance ferroptosis in both cell types, promoting antigen presentation and cytotoxic T cell infiltration. Furthermore, combinatorial treatment with an anti-PD-L1 antibody suppresses metastasis and tumor recurrence. Thus, our nanoparticle-based dual-target strategy induces synergistic ferroptosis-immunotherapy in HCC, and represents a promising strategy to sensitize tumors to SF treatment, driving the remodeling of the immunosuppressive tumor microenvironment.