Mitochondria are highly involved in the metastasis of cancer cells. However, low permeability of mitochondria impedes the entry of anti‐cancer drugs. Here, a self‐assembled nanoparticle platform is designed that not only targets the DNA‐intercalating agent doxorubicin to mitochondria but also enhances the specific penetration by opening the mitochondrial permeability transition pores (MPTPs). With drastic improvement in mitochondrial uptake, the drug delivery system results in substantial mitochondrial impairment leading to amplified induction of apoptosis, depletion of energy supply, and inhibition of numerous metastasis‐associated proteins. As a consequence, the drug delivery system significantly inhibits the orthotopic tumor growth, and suppressed the metastasis of cancer cells detached from primary tumors. Additionally, the nanoparticle exhibits a potent effect on eradicating the metastasis of disseminated tumor cell from blood to lung. The results show that strategies of targeting mitochondria and unlocking MPTP are feasible and beneficial to mitigate both tumorigenesis and metastasis.

中文翻译：

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靶向打开线粒体渗透性转变孔可增强纳米颗粒药物输送并减轻癌症转移

线粒体高度参与癌细胞的转移。然而，线粒体的低通透性阻碍了抗癌药物的进入。在这里，设计了一个自组装纳米颗粒平台，不仅可以将 DNA 嵌入剂阿霉素靶向线粒体，还可以通过打开线粒体通透性转换孔（MPTP）来增强特定渗透。随着线粒体摄取的显着改善，药物输送系统会导致线粒体严重受损，从而导致细胞凋亡的诱导放大、能量供应的耗尽以及许多转移相关蛋白的抑制。结果，药物递送系统显着抑制原位肿瘤生长，并抑制从原发肿瘤脱离的癌细胞的转移。此外，纳米颗粒对消除播散性肿瘤细胞从血液到肺部的转移具有有效的作用。结果表明，靶向线粒体和解锁 MPTP 的策略是可行的，并且有利于减轻肿瘤发生和转移。