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In this study mesoporous silica SBA-15 was evaluated as a vehicle for the transport of cytotoxic natural product emodin (EO). SBA-15 was loaded with different quantities of EO (SBA-15|EO1–SBA-15|EO5: 8–36%) and characterized by traditional methods. Several parameters (stabilities) and the in vitro behavior on tumor cell lines (melanoma A375, B16 and B16F10) were investigated. SBA-15 suppresses EO release in extremely acidic milieu, pointing out that EO will not be discharged in the stomach. Furthermore, SBA-15 protects EO from photodecomposition. In vitro studies showed a dose dependent decrease of cellular viability which is directly correlated with an increasing amount of EO in SBA-15 for up to 27% of EO, while a constant activity for 32% and 36% of EO in SBA-15 was observed. Additionally, SBA-15 loaded with EO (SBA-15|EO3) does not disturb viability of peritoneal macrophages. SBA-15|EO3 causes inhibition of tumor cell proliferation and triggers apoptosis, connected with caspase activation, upregulation of Bax, as well as Bcl-2 and Bim downregulation along with amplification of poly-(ADP-ribose)-polymerase (PARP) cleavage fragment. Thus, the mesoporous SBA-15 is a promising carrier of the water-insoluble drug emodin.

Glioblastoma (GBM) is the most frequent and deadly form of primary malignant brain tumor among adults. A promising emerging approach for GBM treatment may be offered from HIV protease inhibitors (HIV-PIs). In fact, in addition to their primary pharmacological activity in the treatment of HIV infection, they possess important anti-neoplastic effects. According to previous studies, the addition of a nitric oxide (NO) donating group to parental compounds can reduce their toxicity and enhance the anticancer action of various compounds, including HIV-PIs. In this study we compared the effects of the HIV-PI Lopinavir (Lopi) and of its NO-derivative Lopinavir-NO (Lopi-NO) on the in vitro growth of LN-229 and U-251 human GBM cell lines. Lopi-NO reduced the viability of LN-229 and U-251 cells at significantly lower concentrations than the parental drug. In particular, Lopi-NO inhibited tumor cell proliferation and induced the differentiation of U-251 cells toward an astrocyte-like phenotype without triggering significant cell death in both cell types. The anticancer effect of Lopi-NO was persistent even upon drug removal. Furthermore, Lopi-NO induced strong autophagy that did not appear to be related to its chemotherapeutic action. Overall, our results suggest that Lopi-NO could be a potential effective anticancer drug for GBM treatment.

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