Herein,
we report facile theranostic platinum nanoparticles (PtNPs)
conjugated to an anticancer drug, doxorubicin (DOX), in unraveling
the inhibition of a cell survival PI3K/AKT (phosphatidylinositol 3-kinase/protein
kinase B) signaling pathway in MCF-7 and MDA-MB-231 human breast cancer
cells. The significant features of our DOX@PtNPs as a theranostic
platform are as follows: (i) drug release studies showed a progressive
pH-dependent delivery; (ii) in vitro studies of DOX@PtNPs
displayed a relatively higher cytotoxicity to breast cancer cells
compared to unconjugated PtNPs and DOX; (iii) intracellular drug release
studies showed a specific binding of DOX@PtNPs and their release within
the cytoplasm and perinuclear region; (iv) DOX@PtNPs induced the apoptosis
of cancer cells by DNA damage via the generation
of elevated levels of reactive oxygen species and decreased mitochondrial
membrane potential (ΔΨm), as evidenced by fluorescence
microscopic studies; and (v) DOX@PtNPs inhibited the PI3K/AKT signaling
pathway in breast cancer cells by activating PTEN, a tumor suppressor
gene. The induced mitochondrial-dependent apoptotic pathway led to
the activation of downstream caspases. Finally, our findings illustrate
that DOX@PtNPs may serve as a better theranostic agent for cancer
nanomedicine.
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