Menthol-modified BSA nanoparticles for glioma targeting therapy using an energy restriction strategy

Current chemotherapeutics for glioma are not sufficiently effective due to their low tolerance and poor blood–brain barrier (BBB) permeability. Energy restriction based on co-delivery of albendazole (Abz) and nano-silver has been proven to suppress tumor growth without adverse effects. Accordingly, menthol was conjugated to BSA (MeB) to overcome the BBB-permeability issue. In this study, Abz-loaded MeB-silver nanoparticles (MBS-Abz) were developed by self-assembly of MeB, albendazole and nano silver for glioma targeting therapy. The nanoparticle entered the brain across the BBB and specifically accumulated in the glioma region. MeB delivered the nanoparticles across the brain capillary endothelial cell monolayer by promoting internalization and BBB disruption. MBS-Abz hindered ATP generation via the inhibition of glycolytic and mitochondrial pathways both in vitro and in vivo. The anti-glioma mechanisms of energy restriction were related to the cytotoxicity, proliferation inhibition, cell cycle arrest, and apoptosis induced by ATP exhaustion, and the effects of MBS-Abz were significantly better than those induced by monotherapy nanoparticles or unmodified nanoparticles. These results demonstrated that by combining the energy restriction effect of albendazole and nano silver, as well as the BBB penetration ability of menthol, MBS-Abz achieves superior anti-glioma efficacy and can be an effective strategy for glioma therapy.