三阴性乳腺癌（TNBC）细胞通过劫持细胞凋亡来抵抗化疗。铁死亡等替代细胞死亡形式提供了新的治疗选择。探索了通过基于白蛋白的纳米载体（N-S Alb NP）使用来拉替尼（NTB；铁死亡诱导剂）和水飞蓟宾（SLB；凋亡诱导剂）的联合疗法来靶向 TNBC。 N-S Alb NP 具有最佳尺寸 (134.26±10.23 nm)、PDI (0.224±0.01) 和％包封率（NTB 约为 80%，SLB 约为 87%）。透射电子显微镜证实了它们的球形形状。体外释放研究表明药物持续释放且无溶血风险。 N-S Alb NPs 比单一药物或其混合物具有更高的细胞摄取和细胞毒性。 N-S Alb NPs 的 IC50 值在 MDA-MB-231（~2.23 倍）和 4T1（~1.85 倍）细胞系中显着降低，凋亡指数在 MDA-MB-231（~1.31 倍）和 4T1（~1.85 倍）细胞系中显着升高。 4T1 细胞系（~1.35 倍）是两种药物的物理混合物（NTB SLB）的结果。 N-S Alb NPs 产生更多的活性氧 (ROS) 并引起线粒体膜去极化，表明细胞死亡增加。他们还通过减少 TNBC 细胞中的谷胱甘肽 (GSH)、增加 Fe2 活性和 MDA 水平，表现出更好的铁死亡诱导作用。因此，N-S Alb NP 具有促进“混合”型细胞死亡的能力，在增强有效负载能力和 TNBC 靶向方面显示出前景。版权所有 © 2023。由 Elsevier B.V 出版。

Triple negative breast cancer (TNBC) cells resist chemotherapy by hijacking apoptosis. Alternative cell death forms like ferroptosis offer new treatment options. A combined therapy using neratinib (NTB; ferroptosis inducer) and silibinin (SLB; apoptosis inducer) via albumin-based nanocarriers (N-S Alb NPs) was explored to target TNBC. N-S Alb NPs had optimal size (134.26±10.23 nm), PDI (0.224±0.01), and % entrapment efficiency (∼80% for NTB and ∼87% for SLB). Transmission electron microscopy confirmed their spherical shape. In vitro release studies showed sustained drug release without hemolysis risk. N-S Alb NPs had higher cellular uptake and cytotoxicity than individual drugs or their mixture. IC50 values for N-S Alb NPs were significantly reduced in MDA-MB-231 (∼2.23-fold) and 4T1 (∼1.85-fold) cell lines and apoptosis index were significantly higher in MDA-MB-231 (∼1.31-fold) and 4T1 cell line (∼1.35-fold) than the physical mixture of both drugs (NTB+SLB). N-S Alb NPs generated more reactive oxygen species (ROS) and caused mitochondrial membrane depolarization, indicating increased cell death. They also exhibited better ferroptosis induction by reducing glutathione (GSH), increasing Fe2+ activity and MDA levels in TNBC cells. Thus, N-S Alb NPs had the ability to promote "mixed" type cell death, showed promise in enhancing the payload capabilities and targeting in TNBC.Copyright © 2023. Published by Elsevier B.V.