肿瘤细胞治疗研究
英文原题：NK cell biomimetic MOF nanoplatform disrupts hypoxia adaption for complete tumor ablation.
该设计使 NKAMP 能够同时克服物理、免疫和缺氧屏障，实现 3.04 倍的肿瘤蓄积提升和 71.88% 的 HIF-1 抑制。
由于免疫抑制和缺氧微环境，三阴性乳腺癌（TNBC）仍是治疗难题。我们开发了NKAMP仿生纳米平台，通过三种协同机制克服免疫逃逸和缺氧耐受：（1）利用NK细胞膜上的CD226/NKG2D与MUC1适配体实现智能双靶向，确保强效且冗余的靶向；（2）释放药物以抑制HIF-1功能并破坏缺氧适应；（3）实施免疫相容性光动力疗法（PDT）。该设计使NKAMP能够同时克服物理、免疫和缺氧屏障，使肿瘤蓄积量提高3.04倍，并抑制HIF-1达71.88%。破坏缺氧适应后形成自增强的活性氧放大循环（增加1.53倍），诱导线粒体凋亡，并在体内实现肿瘤完全消融（体积减少96.16%）；与单用PCN-224相比，疗效提高10.9倍。该平台通过免疫相容性PDT重编程肿瘤微环境，建立了一种新的免疫相容性PDT范式，以应对TNBC相互交织的多重挑战。
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-1 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-1 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.
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