tailieunhanh - Delivery of chemotherapeutic agents using drug-loaded irradiated tumor cells to treat murine ovarian tumors

Ovarian cancer is the leading cause of death among women with gynecologic malignancies in the United States. Advanced ovarian cancers are difficult to cure with the current available chemotherapy, which has many associated systemic side effects. Doxorubicin is one such chemotherapeutic agent that can cause cardiotoxicity. Novel methods of delivering chemotherapy without significant side effects are therefore of critical need. Methods: In the current study, we generated an irradiated tumor cell-based drug delivery system which uses irradiated tumor cells loaded with the chemotherapeutic drug, doxorubicin. Results: We showed that incubation. | Kim et al. Journal of Biomedical Science 2010 17 61 http content 17 1 61 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Delivery of chemotherapeutic agents using drug-loaded irradiated tumor cells to treat murine ovarian tumors 1 13 3 Daejin Kim1 4 Talia Hoory1 Archana Monie1 Annie Wu3 Wei-Ting Hsueh Sara I Pai3 Chien-Fu Hung1 Abstract Background Ovarian cancer is the leading cause of death among women with gynecologic malignancies in the United States. Advanced ovarian cancers are difficult to cure with the current available chemotherapy which has many associated systemic side effects. Doxorubicin is one such chemotherapeutic agent that can cause cardiotoxicity. Novel methods of delivering chemotherapy without significant side effects are therefore of critical need. Methods In the current study we generated an irradiated tumor cell-based drug delivery system which uses irradiated tumor cells loaded with the chemotherapeutic drug doxorubicin. Results We showed that incubation of murine ovarian cancer cells MOSEC with doxorubicin led to the intracellular uptake of the drug MOSEC-dox cells and the eventual death of the tumor cell. We then showed that doxorubicin loaded MOSEC-dox cells were able to deliver doxorubicin to MOSEC cells in vivo. Further characterization of the doxorubicin transfer revealed the involvement of cell contact. The irradiated form of the MOSEC-dox cells were capable of treating luciferase-expressing MOSEC tumor cells MOSEC luc in C57BL 6 mice as well as in athymic nude mice resulting in improved survival compared to the non drug-loaded irradiated MOSEC cells. Furthermore we showed that irradiated MOSEC-dox cells was more effective compared to an equivalent dose of doxorubicin in treating MOSEC luc tumor-bearing mice. Conclusions Thus the employment of drug-loaded irradiated tumor cells represents a .