Poster #081, CHLA LA-HIP
Targeted Micelles Delivery of PI3K, AKT, and mTOR inhibitors in Wilms Tumor Cancer Stem Cells as a Novel Therapeutic Strategy
Mentors: Osanna Kosoyan, MS and Laura Perin, PhD
Wilms tumor (WT) is the most common kidney cancer in young children. While current treatments such as chemotherapy, radiation, and surgery have improved survival rates, they
also affect both healthy and cancer cells, thus increasing toxicity. This project explores a targeted treatment approach using CCR2-targeted micelles to deliver drugs directly to Wilms tumor cancer stem cells (WT-CSCs). We hypothesized that these targeted micelles can be selectively uptaken by the WT-CSCs thus reducing cancer cell growth. WT total population cells were treated with fluorescently labeled CCR2-targeted and non-targeted micelles, and FACS sorting was used to evaluate cell uptake dynamics. Since WT-CSC highly express the PI3K/AKT/mTOR pathway, they were exposed to micelles loaded with PI3K, AKT, or mTOR inhibitors and western blot analysis was used to measure changes in expression of PI3K/AKT/mTOR signaling pathway after treatment. CCR2-targeted micelles showed greater uptake compared to non-targeted micelles. Treatment with drug-loaded micelles decreased expression of PI3K/AKT/mTOR pathway as well as the stem cell markers SIX2 and CITED1, suggesting successful drug delivery to the cancer cells.These findings suggest that CCR2-targeted micelles may provide a more effective and targeted approach to treating Wilms tumor by delivering drugs directly to cancer stem cells while reducing damage to healthy tissue. This approach has the potential to improve future treatments for children with Wilms tumor.