Delivery of chemotherapeutic agents using drug-loaded irradiated tumor cells to treat murine ovarian tumors.
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 potentially innovative approach for the delivery of chemotherapeutic drugs for the control of ovarian tumors.
Kim
Daejin
D
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Hoory
Talia
T
Monie
Archana
A
Wu
Annie
A
Hsueh
Wei-Ting
WT
Pai
Sara I
SI
Hung
Chien-Fu
CF
D000818:Animals; D004317:Doxorubicin / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004337:Drug Carriers / Q000627:therapeutic use*; D004358:Drug Therapy / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D008156:Luciferases; D051379:Mice; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects
D004337:Drug Carriers; D004317:Doxorubicin; D008156:Luciferases