Scholarlink

<p>The clinical therapeutic effect of immune-checkpoint blockade (ICB) on triple-negative breast cancer (TNBC) is limited due to low tumor immunogenicity and tumor immunosuppressive microenvironment. Combination therapies of chemotherapy and ICB have been confirmed efficacious. Herein, poly(L-lysine) dendrimer (PLLD) nanosphere (PR-T@PLLD) integrating chemotherapeutic drug paclitaxel (PTX), natural anti-tumor compound Rubioncolin C (RC) and TIGIT/PVR blocking peptide <sup>D</sup>TBP-3 is constructed for chemo-immunotherapy of anti-PD-1 resistant tumor. The PEGylation and <sup>D</sup>TBP-3 modification endow PR-T@PLLD with prolonged blood circulation, enhanced tumor penetration and improved internalization. In the acidic environment of lysosomes, PR-T@PLLD disassembles and releases PTX, RC and <sup>D</sup>TBP-PLLD. The cell death induced by PTX is significantly enhanced through synergy with RC. RC collaborated PTX also triggers robust immunogenic cell death that efficiently increases tumor infiltration of cytotoxic T lymphocytes (CTLs). Additionally, the released <sup>D</sup>TBP-PLLD inhibits the exhaustion of CTLs via directly binding to TIGIT and blocking the interaction of TIGIT with its ligand PVR. Thus, PR-T@PLLD arouses a conspicuous anti-tumor immune response via increasing income and reducing expenditure of CTLs. Moreover, PR-T@PLLD reduces the recruitment of immunosuppressive cells in tumor. PR-T@PLLD also inhibits tumor metastasis through evoking immune memory response and inhibiting epithelial-mesenchymal transition and extracellular matrix degradation. In general, PR-T@PLLD is a promising nanoplatform realizing synergistic enhancement of chemo-immunotherapy against anti-PD-1 resistant TNBC.</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

Tumor targeting dendritic nanocarrier with immunogenic cell death inducing and TIGIT blockade for synergistic chemo-immunotherapy against TNBC

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月7日

查看全文
  • Jia Wang,
  • Zhiji Wang,
  • Kaiming Li,
  • Yue Liu,
  • Chunming Tang,
  • Huimin Gao,
  • Yupeng Zhou,
  • Pengpeng Wang,
  • Haisi Wu,
  • Pengfei Liu,
  • Huae Xu,
  • Xiaolin Li

摘要

The clinical therapeutic effect of immune-checkpoint blockade (ICB) on triple-negative breast cancer (TNBC) is limited due to low tumor immunogenicity and tumor immunosuppressive microenvironment. Combination therapies of chemotherapy and ICB have been confirmed efficacious. Herein, poly(L-lysine) dendrimer (PLLD) nanosphere (PR-T@PLLD) integrating chemotherapeutic drug paclitaxel (PTX), natural anti-tumor compound Rubioncolin C (RC) and TIGIT/PVR blocking peptide DTBP-3 is constructed for chemo-immunotherapy of anti-PD-1 resistant tumor. The PEGylation and DTBP-3 modification endow PR-T@PLLD with prolonged blood circulation, enhanced tumor penetration and improved internalization. In the acidic environment of lysosomes, PR-T@PLLD disassembles and releases PTX, RC and DTBP-PLLD. The cell death induced by PTX is significantly enhanced through synergy with RC. RC collaborated PTX also triggers robust immunogenic cell death that efficiently increases tumor infiltration of cytotoxic T lymphocytes (CTLs). Additionally, the released DTBP-PLLD inhibits the exhaustion of CTLs via directly binding to TIGIT and blocking the interaction of TIGIT with its ligand PVR. Thus, PR-T@PLLD arouses a conspicuous anti-tumor immune response via increasing income and reducing expenditure of CTLs. Moreover, PR-T@PLLD reduces the recruitment of immunosuppressive cells in tumor. PR-T@PLLD also inhibits tumor metastasis through evoking immune memory response and inhibiting epithelial-mesenchymal transition and extracellular matrix degradation. In general, PR-T@PLLD is a promising nanoplatform realizing synergistic enhancement of chemo-immunotherapy against anti-PD-1 resistant TNBC.

Graphical Abstract