Transcription factor complex NF-κB (p65/p50) is localized to the cytoplasm by its inhibitor IκBα. Upon activation, the Rel proteins p65/p50 are released from IκBα and transported through nuclear pore to effect many gene expressions. While inhibitions of up or down stream signal pathway are often ineffective due to crosstalks and compensations, direct blocking of the Rel proteins p65/p50 has long been proposed as a potential target for cancer therapy. In this work, a nanoparticle/antibody complex targeting NF-κB is employed to catch the Rel protein p65 in perinuclear region and thus blocking the translocation near the nuclear pore gate. TAT peptide conjugated on mesoporous silica nanoparticles (MSN) help non-endocytosis cell-membrane transducing and converge toward perinuclear region, where the p65 specific antibody performed the targeting and catching against active NF-κB p65 effectively. The size of the p65 bound nanoparticle becomes too big to enter nucleus. Simultaneous treatment of mice with the hybrid MSN and doxorubicin conferred a significant therapeutic effect against 4T1 tumor-bearing mice. The new approach of anti-body therapy targeting on transcription factor with “nucleus focusing” and “size exclusion blocking” effects of the antibody-conjugated nanoparticle is general and may be applicable to modulating other transcription factors.

转录因子复合物NF-κB（p65 / p50）通过其抑制剂IκBα定位于细胞质。激活后，Rel蛋白p65 / p50从IκBα中释放出来并通过核孔运输，从而影响许多基因表达。尽管由于串扰和补偿作用，对上游或下游信号通路的抑制作用通常无效，但长期以来一直提出直接阻断Rel蛋白p65 / p50作为癌症治疗的潜在靶标。在这项工作中，采用靶向NF-κB的纳米颗粒/抗体复合物在核周区域捕获Rel蛋白p65，从而阻止了核孔门附近的转运。结合在中孔二氧化硅纳米颗粒（MSN）上的TAT肽有助于非内吞作用细胞膜转导并向核周区域汇聚，其中p65特异性抗体有效地靶向和捕获了活性NF-κBp65。与p65结合的纳米颗粒的尺寸太大，无法进入核。用杂种MSN和阿霉素同时治疗小鼠对具有4T1肿瘤的小鼠具有显着的治疗作用。针对抗体结合的纳米颗粒具有“细胞核聚焦”和“尺寸排阻阻断”作用的转录因子的抗体疗法新方法是通用的，可能适用于调节其他转录因子。