GO-loaded Valrubicin(AD32) Inhibit Intracerebral Melanomas In Mice

In spite of the advancements of the technology for cancer treatment, caner is one of the major health-threating diseases all over the world. Brain tomor is primary cancer, and can be induced to develop as the intracerebral metastatic cancer. Usually, metastatic cancer is very invasive and the survival of patients after therapy is very poor.In the course of screening new drugs against intracerebral metastatic melanoma, we found that valrubicin (AD32) has potent cytotoxic activity against mice melanoma, B16 cells. However, the antitumor activity in brain was not significant. Therefore, in this work, we developed two kinds of nanoparticles, multi-wall carbon nano tubes (MWCNTs) and graphene oxide(GO), and loaded with AD32 to form nano medicines for the treatment of intracerebral metastatic melanoma in mice. Results indicated that MWCNTs and GO can increase the antitumor activity in intracerebral melanoma. However, AD32-MWCNTs showed some light neurocirulence to mice. By contrast, AD32-GO showed the most potent antitumor activities without any neurocirulence. Further experiments showed GO may deliver AD32 by pH sensitivity, and the participation of GO accelerated the speed of AD32 entering into cell nucleus, it also increased the drug absorption within tumor cells and reduced the drug elimination induced by resistence mechanism of tumor cell, thus the generation of ROS was increased and cell cycle resistance was induced. Synthetic drug AD32-GO overcame the barriers of the poor water-solubility of AD32 and showed a stronger cytotoxicity to cancer cells than free AD32. AD32-GO also enhanced the anti tumor activity to intracerebral melanoma in mice. Whole results suggested that GO is an effective and safe drug carrier, and AD32-GO is a potent and safe nano medicine in the treatment of intracerebral melanoma in mice.