Abstract
Metal and its oxide nanoparticles show ideal pharmacological activity, especially in anti-tumor therapy. Our previous study demonstrated that cuprous oxide nanoparticles (CONPs) selectively induce apoptosis of tumor cells in vitro. To explore the anti-tumor properties of CONPs in vivo, we used the particles to treat mouse subcutaneous melanoma and metastatic lung tumors, based on B16-F10 mouse melanoma cells, by intratumoral and systemic injections, respectively. The results showed that CONPs significantly reduced the growth of melanoma, inhibited the metastasis of B16-F10 cells and increased the survival rate of tumor-bearing mice. Importantly, the results also indicated that CONPs were rapidly cleared from the organs and that these particles exhibited little systemic toxicity. Furthermore, we observed that CONPs targeted the mitochondria, which resulted in the release of cytochrome C from the mitochondria and the activation of caspase-3 and caspase-9 after the CONPs entered the cells. In conclusion, CONPs can induce the apoptosis of cancer cells through a mitochondrion-mediated apoptosis pathway, which raises the possibility that CONPs could be used to cure melanoma and other cancers.
Highlights
Arsenic trioxide, which represents one of the new types of medicines and is derived from a famous, traditional Chinese remedy, has been used to successfully treat acute promyelocytic leukemia.[13]
The other reason is that our previous research has shown that cuprous oxide nanoparticles (CONPs) can selectively induce apoptosis and inhibit the proliferation of tumor cells in vitro and that melanoma cells are highly sensitive to CONPs,[19] suggesting that CONPs may be used in the treatment of melanoma
We found that CONPs without chemical modification targeted the mitochondria caused cytochrome C (Cyt C) release, and activated caspase[3] and caspase-9, which demonstrated that CONPs induced
Summary
Arsenic trioxide, which represents one of the new types of medicines and is derived from a famous, traditional Chinese remedy, has been used to successfully treat acute promyelocytic leukemia.[13]. Melanoma is a cancer that is difficult to cure by conventional therapy, which is one of the reasons why we chose to focus on melanoma in this study.[16,17,18] The other reason is that our previous research has shown that CONPs can selectively induce apoptosis and inhibit the proliferation of tumor cells in vitro and that melanoma cells are highly sensitive to CONPs,[19] suggesting that CONPs may be used in the treatment of melanoma To verify this hypothesis, we sought to test the anti-tumor capability of CONPs in vivo. We found that CONPs without chemical modification targeted the mitochondria caused cytochrome C (Cyt C) release, and activated caspase[3] and caspase-9, which demonstrated that CONPs induced
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