PROJECT SUMMARY Ovarian cancer is the fifth most common cause of cancer-related deaths in women and results in more deaths than any other cancer of the female reproductive system. The primary reason for the high death rate of ovarian cancer is multidrug-resistance. Since conventional anticancer drugs cannot kill drug-resistant cells while causing systemic toxicity to deteriorate patient health condition, a novel effective and safe treatment for ovarian cancer is urgently needed. Our preliminary study has discovered a novel polymer-metal combination which uniquely induces a lysosomal copper elevation initiated intrinsic apoptosis pathway. Consequently, this combination is highly selectively in killing cancer cells, including drug-resistant ovarian cancer cells, while not damaging healthy cells. The objective of this research is to develop a polymer-metal nano-complex (PMC) for safe and effective ovarian cancer therapy through a cancer cell selective apoptosis mechanism. Our project has three specific aims. In Aim 1, we will identify the mechanism of cancer cell killing effect of PMC. Aim 2 will identify the cancer selective killing mechanism of PMC and optimize its formulation to achieve the highest selectivity for cancer cells. Aim 3 will investigate the pharmacokinetic properties, examine the biodistribution of PMC, and evaluate its tumor growth inhibitory effect, immune response, and systemic toxicity. In summary, the unique anticancer mechanism of PMC and its simple formulation will provide clinicians a safe and effective tool to control advanced ovarian cancer and benefit ovarian cancer patients.