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.