PEPTOID-PEPTIDE HYBRID FOR SELECTIVE TARGETING AND ELIMINATION OF BREAST CANCER STEM CELLS

Breast cancer remains one of the deadliest diseases in the world and poses a great threat due to its resistance to common chemotherapeutics. Recent studies propose the theory of cancer stem cells, a subpopulation of self-renewing progenitors as the root cause of therapy resistance. The presence of cancer stem cells explains the occurrence of tumor relapses as they would continue to self-renew after initial treatment. Due to this challenge, development of a novel therapeutic to target and eliminate cancer stem cells is a promising strategy for increasing survival rate in breast cancer patients. Previous studies have discovered a synthetic peptoid, CL-1-19-1, that binds to breast cancer stem cells in high affinity. In conjugation with the killer-peptide sequence D(KLAKLAK)2, a “hunter-killer” peptide (CKP) to target and eliminate breast cancer stem cells was synthesized. Preliminary results show that CKP can decrease cell viability via induction of apoptosis and inhibit tumorsphere formation in breast cancer cell lines. To further characterize and optimize the efficacy of CKP, we have conducted circular dichroism spectroscopy and a calcein dye leakage assay. It was found that CKP adopts an α-helical structure as a necessity in inducing its mechanism of action. Leakage of calcein dye from a mitochondrial membrane memetic increased as concentration of CKP increased confirming its ability to permeabilize lipid membrane. Future studies involve synthesizing derivatives of CKP that increase its α-helical characteristics to efficiently induce apoptosis in breast cancer stem cells.