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Abstract
Introduction Cisplatin is the most used drug in chemotherapy. We presented a novel synthesized Nano-Platinum (NanoPt) for the treatment of ovarian cancer and explores its antitumor effects.
Methods The morphology of NanoPt was characterized by transmission electron microscopy. It was labeled with the fluorophore Cy5.5 and incubated with OV8 cells to investigate cellular uptake using confocal laser scanning microscopy (CLSM). The intracellular distributions were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The antitumor mechanism was evaluated in vitro through proliferation assay and apoptosis assay. The antitumor efficacy was examined in vivo by PDX model.
Results NanoPt have an average diameter of about 80nm and displayed a spherical morphology (figure 1). It is indicated an increase in red fluorescence within cells over time with Cy5.5@NanoIr incubation((figure 2)). OV8 cells were treated with NanoPt and tracked at 0.5, 1, and 3 h with an increase in NanoPt content over time (figure 3). Notably, NanoPt demonstrated greater cellular entry into tumor cells compared to cisplatin, with a significant portion localizing in the mitochondria. NanoPt was observed to induce more cell death at the same concentration compared to cisplatin (figure 4) and resulted in a higher rate of cell apoptosis (41%) than cisplatin (5%) (figure 5). PDX showed NanoPt (10mg/kg) significantly suppressing tumor progression (88.3%) without signs of pain, stress or weight loss compared to Cisplatin of moderate tumor inhibition (49.6%).
Conclusion/Implications The advanced synthetic nano platinum developed in this study enhances cisplatin accumulation in ovarian cancer cells, leading to an improved antitumor effect.
