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<p>Immune checkpoint blockade (ICB) has advanced melanoma therapy, yet its efficacy remains limited by poor tumor immunogenicity and insufficient T-cell infiltration. To overcome these dual barriers, we develop BPC9@MnCO<sub>3</sub>, a biomimetic nanoplatform cloaked with PD-1-enriched melanoma membranes and loaded with chemokine CXCL9. The tumor-homing membrane coating directs nanoparticle accumulation in melanoma tissue. Additionally, PD-1 overexpression on the surface of B16-F10 cell membranes blocks the PD-1/PD-L1 signaling axis, thereby restoring T-cell immune function. Within the acidic tumor microenvironment, MnCO<sub>3</sub> decomposes to release Mn<sup>2+</sup> ions, which trigger immunogenic cell death (ICD) to enhance tumor antigen presentation. Meanwhile, the degradation of MnCO<sub>3</sub> triggers membrane rupture, which increases local CXCL9 levels and leads to enhanced T-cell infiltration, thereby mediating a potent antitumor immune response. Notably, BPC9@MnCO<sub>3</sub> significantly inhibits tumor growth and reduces the number of lung metastases in vivo. These effects are attributed to the ability of BPC9@MnCO<sub>3</sub> to relieve immune checkpoint inhibition and induce ICD effects, effectively improving the immune microenvironment and significantly enhancing T-cell infiltration in tumor tissue. In summary, our work demonstrates a novel strategy to improve ICB efficacy by coordinately targeting immune activation and recruitment barriers.</p>

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PD-1-engineered manganese-based nanoplatform loaded with CXCL9 induces ICD and intensifies T-cell infiltration for melanoma treatment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月9日

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  • Penglong Ma,
  • Jueshuo Guo,
  • Li Peng,
  • Ting Gao,
  • Na Yu,
  • Tingting Fu,
  • Jianhong Yang

摘要

Immune checkpoint blockade (ICB) has advanced melanoma therapy, yet its efficacy remains limited by poor tumor immunogenicity and insufficient T-cell infiltration. To overcome these dual barriers, we develop BPC9@MnCO3, a biomimetic nanoplatform cloaked with PD-1-enriched melanoma membranes and loaded with chemokine CXCL9. The tumor-homing membrane coating directs nanoparticle accumulation in melanoma tissue. Additionally, PD-1 overexpression on the surface of B16-F10 cell membranes blocks the PD-1/PD-L1 signaling axis, thereby restoring T-cell immune function. Within the acidic tumor microenvironment, MnCO3 decomposes to release Mn2+ ions, which trigger immunogenic cell death (ICD) to enhance tumor antigen presentation. Meanwhile, the degradation of MnCO3 triggers membrane rupture, which increases local CXCL9 levels and leads to enhanced T-cell infiltration, thereby mediating a potent antitumor immune response. Notably, BPC9@MnCO3 significantly inhibits tumor growth and reduces the number of lung metastases in vivo. These effects are attributed to the ability of BPC9@MnCO3 to relieve immune checkpoint inhibition and induce ICD effects, effectively improving the immune microenvironment and significantly enhancing T-cell infiltration in tumor tissue. In summary, our work demonstrates a novel strategy to improve ICB efficacy by coordinately targeting immune activation and recruitment barriers.