Targeted Polymeric Parthenolide Carriers to Treat Childhood AML
With chemotherapy treatment, 80-90% of children with acute myeloid leukemia (AML) achieve remission. However, 30-40% of these patients subsequently suffer recurrence, and the long-term survival rate is only 50%. Novel therapies are urgently needed to prevent or treat recurring AML. Parthenolide, a naturally-occurring compound, induces robust AML cell killing and has the potential to reduce recurrence of AML by killing cells resistant to traditional chemotherapeutics and responsible for relapse. However, parthenolide's development as a chemotherapeutic drug has been limited due to low solubility. Therefore, we aim to develop polymer delivery systems to increase parthenolide solubility and enable its use therapeutically. These polymers will be designed to self-assemble into three-dimensional spheres with cores to entrap parthenolide and shells to enhance solubility. To provide specificity to polymer carriers, we will incorporate targeting groups that home directly to AML cells to localize drug release at cells responsible for recurrence of AML. Carriers with different properties including parthenolide loading and release will be evaluated for AML cell killing using established in vitro and in vivo models. The dose and dosing regime will also be modified to achieve the greatest AML cell killing. This approach will provide for more effective treatments for childhood AML, resulting in lower rates of relapse and reduction of overall mortality.