Scholarlink

<p>The combination of chemotherapy and immune checkpoint blockade therapy shows great potential in tumor treatment, but their integration remains a great challenge. Herein, hypoxia-responsive prodrugs integrating paclitaxel (PTX) and bromodomain-containing protein 4 inhibitor JQ1 were designed and fabricated into nanoparticles (DJNP NPs) in the presence of DSPE-PEG<sub>2000</sub>. After accumulation at the tumor site, DJNP NPs can respond to tumor hypoxic condition and trigger the release of PTX and JQ1. The released PTX can result in cell apoptosis, which further evokes immunogenic cell death to boost the intratumoral infiltration of cytotoxic T lymphocytes. Meanwhile‌, overexpression of programmed cell death ligand 1 (PD-L1) is suppressed by JQ1, thereby reversing PD-L1-mediated immune resistance to synergistically promote adaptive antitumor immune response. This hypoxia-sensitive versatile nanoplatform provides an elegant paradigm for precise tumor therapy.</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

Hypoxia-activated paclitaxel prodrugs enable PD-L1 degradation to potentiate cancer chemo-immunotherapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月2日

查看全文
  • Shiyu Zhou,
  • Qiang Zhang,
  • Hui Han,
  • Guang Chen,
  • Peisong Wang,
  • Shuai Xue,
  • Qing Pei,
  • Zhigang Xie,
  • Xianying Meng

摘要

The combination of chemotherapy and immune checkpoint blockade therapy shows great potential in tumor treatment, but their integration remains a great challenge. Herein, hypoxia-responsive prodrugs integrating paclitaxel (PTX) and bromodomain-containing protein 4 inhibitor JQ1 were designed and fabricated into nanoparticles (DJNP NPs) in the presence of DSPE-PEG2000. After accumulation at the tumor site, DJNP NPs can respond to tumor hypoxic condition and trigger the release of PTX and JQ1. The released PTX can result in cell apoptosis, which further evokes immunogenic cell death to boost the intratumoral infiltration of cytotoxic T lymphocytes. Meanwhile‌, overexpression of programmed cell death ligand 1 (PD-L1) is suppressed by JQ1, thereby reversing PD-L1-mediated immune resistance to synergistically promote adaptive antitumor immune response. This hypoxia-sensitive versatile nanoplatform provides an elegant paradigm for precise tumor therapy.

Graphical Abstract