Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination.

摘要: Breast cancer stem cells (CSC) are thought responsible for tumor growth and relapse, metastization active evasion to standard chemotherapy. The recognition that CSC may originate from non-stem (non-SCC) through plastic epithelial-to-mesenchymal transition turned these into relevant cell targets. Of crucial importance successful therapeutic intervention is the identification of surface receptors overexpressed in both non-SCC. Cell nucleolin has been described as well a angiogenic marker. Herein we have addressed questions on whether was common receptor among breast non-SCC it could be exploited targeting purposes. Liposomes functionalized with nucleolin-binding F3 peptide, targeted simultaneously, nucleolin-overexpressing putative non-SCC, which paralleled by OCT4 NANOG mRNA levels triple negative (TNBC) origin. In murine embryonic cells, peptide-targeted liposomes cellular association were dependent stemness status. An in vivo tumorigenic assay suggested overexpression per se, associated highly TNBC cells. This proposed link between expression stem-like phenotype TNBC, enabled 100% death mediated synergistic drug combination, suggesting potential abrogate plasticity adaptability Ultimately, nucleolin-specific tools capable simultaneous debulk multiple compartments microenvironment pave way towards specific treatment patient care.