On the one hand, to obtain a novel next-generation anticancer metal agent; on the other hand, to improve the targeting ability and decrease side effects of metal agent, we proposed to design active-targeting human serum albumin (HSA) nanoparticles (NPs) to achieve the end. Thus, we not only designed and synthesized two ruthenium (Ru) thiosemicarbazone compounds (C1 and C2) but also succeeded in constructing active Biotin-HSA NPs for Ru(III) compounds. Importantly, Biotin-HSA-C2 NPs not only possessed a stronger capacity for killing MCF-7 cells and inhibiting their migration versus C2 alone but also increased accumulation compared to non-malignant WI-38 cells. Additionally, C2 and Biotin-HSA-C2 NPs act against MCF-7 cells by the following potential mechanism: 1) arresting the cell cycle in the S phase by regulating cyclin and cyclin-dependent kinases; 2) inducing apoptosis by releasing cytochrome c to activate caspase-9/3; 3) inhibiting the expression of p-EGFR and regulating its neighboring cellular pathways, followed by the inactivation of PI3K/Akt and activation of p38 MAPK signaling pathways.

一方面，获得新型的下一代抗癌金属剂；另一方面，为了提高靶向能力并减少金属制剂的副作用，我们提出设计主动靶向人血清白蛋白（HSA）纳米颗粒（NPs）来达到目的。因此，我们不仅设计并合成了两种钌 (Ru) 缩氨基硫脲化合物（C1和C2），而且还成功构建了 Ru(III) 化合物的活性生物素-HSA NPs。重要的是，与单独的C2相比，生物素-HSA- C2 NPs 不仅具有更强的杀死 MCF-7 细胞和抑制其迁移的能力，而且与非恶性 WI-38 细胞相比，还具有增加的积累。此外，C2和生物素-HSA- C2 NPs 通过以下潜在机制对 MCF-7 细胞起作用：1) 通过调节细胞周期蛋白和细胞周期蛋白依赖性激酶将细胞周期阻滞在 S 期；2)通过释放细胞色素c激活caspase-9/3诱导细胞凋亡；3）抑制p-EGFR的表达并调节其邻近的细胞通路，进而使PI3K/Akt失活，激活p38 MAPK信号通路。