Glioblastoma multiforme (GBM) is the most prevalent form of brain tumor, which generally has a poor prognosis. According to consensus, recurrence of the tumor and chemotherapy resistance acquisition are the two distinguishing features of GBM originated from glioblastoma stem cells (GSCs). To eliminate these obstacles inherent in GBM chemotherapy, targeting GSCs through a smart drug delivery system has come to the front position of GBM therapeutics. In this study, B19 aptamer (Apt)-conjugated polyamidoamine (PAMAM) G4C12 dendrimer nanoparticles (NPs), called Apt-NPs, were formulated for the co-delivery of paclitaxel (PTX) and temozolomide (TMZ) to U-87 stem cells. These drugs were loaded using a double emulsification solvent evaporation method. As a result, drug-loaded Apt-NPs significantly inhibited the tumor growth of U-87 stem cells, by the initiation of apoptosis via the downregulation of autophagic and multidrug resistance (MDR) genes. Additionally, by their downregulation by qPCR of CD133, CD44, SOX2, and the canonical Wnt/β-catenin pathway, cell proliferation has substantially decreased. Altogether, the results demonstrate that this intelligent drug co-delivery system is capable of effectively transferring PTX and TMZ to U-87 stem cells and without any toxic effect on Apt-NPs alone to U-87 stem cells. Furthermore, the designed dendrimer-based pharmaceutical system along with single-stranded B19 aptamer might be utilized as a new therapeutic strategy for the treatment of U-87 stem cells drug resistance in the GBM.
Keywords: Apoptosis; Autophagy; Co-delivery; Multidrug resistance; Nanocarrier; Wnt/β-catenin.
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