Oleuropein- and hydroxytyrosol-loaded nanoparticles: a novel strategy against glioblastoma aggressiveness

Glioblastoma (GB), the most aggressive type of brain tumor, has a poor prognosis. In this study, we aimed to develop a drug delivery system that can be used in GB treatment with the bioactive compounds oleuropein (OL) and its derivative hydroxytyrosol (HT) loaded into mesoporous silica nanoparticles (MSNs) and to investigate their anticancer effects on GB cells. MSNs were synthesized via a sol‒gel method, followed by surface grafting of azetidine to introduce hyperbranched polypropylene imine (PPI) groups, increasing the particle stability and OL/HT loading efficiency. OL and HT-loaded MSN-PPI nanocarriers (MSN-PPI@OL and MSN-PPI@HT) were characterized, and their effects on tumor aggressiveness were evaluated in T98G cells. The results showed that the nanocarriers presented a positive surface charge and hydrodynamic sizes between 300 and 500 nm, with effective concentrations above 100 µg/mL. MSN-PPI@OL and MSN-PPI@HT alone and in combination with temozolomide (TMZ) inhibited cell migration (p < 0.0001), reduced the expression of epithelial‒mesenchymal transition (EMT) markers (p < 0.05), and suppressed angiogenesis (p < 0.0001). In the colony formation assays, the MSN-PPI nanocarriers had stronger antiproliferative effects than did TMZ (p < 0.0001) and suppressed the expression of stem cell markers (p < 0.05). Additionally, these treatments decreased LOXL1-AS1, PVT1, and MALAT1 expression (p < 0.05) and reduced global cell viability (p < 0.0001). In conclusion, these findings suggest the potential of MSN-PPI@OL and MSN-PPI@HT as effective therapeutic strategies for GB.