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<p>Triple-negative breast cancer (TNBC) remains a therapeutic challenge due to its immunosuppressive and hypoxic microenvironment. We developed NKAMP, a biomimetic nanoplatform that synergistically overcomes immune evasion and hypoxia resistance through three synergistic mechanisms: (1) intelligent dual-targeting (NK cell membrane CD226/NKG2D plus MUC1 aptamer) to ensure robust and redundant targeting, (2) drug release to inhibit HIF-1α function and disrupt hypoxia adaption, and (3) immune-compatible photodynamic therapy (PDT). This design allows NKAMP to overcome physical, immunological, and hypoxic barriers simultaneously, achieving 3.04-fold higher tumor accumulation and 71.88% HIF-1α suppression. The resulting hypoxia adaptation disruption created a self-reinforcing ROS amplification cycle (1.53-fold increase), inducing mitochondrial apoptosis and achieving complete tumor ablation in vivo (96.16% volume reduction) with 10.9 times efficacy improvement than PCN-224 alone. By reprogramming the tumor microenvironment through immune-compatible PDT, this platform establishes a new “immune-compatible PDT” paradigm that addresses TNBC’s intertwined challenges.</p> Graphical Abstract <p></p>

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NK cell biomimetic MOF nanoplatform disrupts hypoxia adaption for complete tumor ablation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月14日

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  • Li Chen,
  • Yang Li,
  • Jingwen Yu,
  • Shuqin Li,
  • Pu Wang,
  • Xiu-Hong Wang

摘要

Triple-negative breast cancer (TNBC) remains a therapeutic challenge due to its immunosuppressive and hypoxic microenvironment. We developed NKAMP, a biomimetic nanoplatform that synergistically overcomes immune evasion and hypoxia resistance through three synergistic mechanisms: (1) intelligent dual-targeting (NK cell membrane CD226/NKG2D plus MUC1 aptamer) to ensure robust and redundant targeting, (2) drug release to inhibit HIF-1α function and disrupt hypoxia adaption, and (3) immune-compatible photodynamic therapy (PDT). This design allows NKAMP to overcome physical, immunological, and hypoxic barriers simultaneously, achieving 3.04-fold higher tumor accumulation and 71.88% HIF-1α suppression. The resulting hypoxia adaptation disruption created a self-reinforcing ROS amplification cycle (1.53-fold increase), inducing mitochondrial apoptosis and achieving complete tumor ablation in vivo (96.16% volume reduction) with 10.9 times efficacy improvement than PCN-224 alone. By reprogramming the tumor microenvironment through immune-compatible PDT, this platform establishes a new “immune-compatible PDT” paradigm that addresses TNBC’s intertwined challenges.

Graphical Abstract