LAUSR

ABSTRACT One of the major challenges in Glioblastoma (GBM) therapy relates with the existence of glioma stem‐like cells (GSCs), known to be chemo‐ and radio‐resistant. GSCs and non‐stem GBM cells have the ability to interchange, emphasizing the importance of identifying common molecular targets among those cell sub‐populations. Nucleolin overexpression has been recently associated with breast cancer sub‐populations with different stem‐like phenotype. The goal of this work was to evaluate the potential of cell surface nucleolin as a target in GBM cells. Different levels of nucleolin expression resulted in a 3.4‐fold higher association of liposomes targeting nucleolin (functionalized with the nucleolin‐binding F3 peptide) in U87, relative to GBM11 glioblastoma cells. Moreover, nucleolin was suggested as a potential marker in OCT4‐, NANOG‐positive GSC, and in the corresponding non‐stem GBM cells, as well as in SOX2‐positive GSC. Doxorubicin delivered by liposomes targeting nucleolin enabled a level of cytotoxicity that was 2.5‐ or 4.6‐fold higher compared to the non‐targeted counterparts. Importantly, an overexpression of nucleolin was also observed in cells of patient‐derived samples, as compared with normal brain. Overall, these results suggested nucleolin as a therapeutic target in GBM. HIGHLIGHTSNucleolin is overexpressed in GSC sub‐populations and non‐stem glioblastoma cells;Nucleolin enables intracellular targeted drug delivery in glioblastoma cells;Nucleolin is overexpressed in glioblastoma patient‐derived samples.