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

Abstract

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.

Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

“…[ 102b ] In particular, albumin greatly enhanced targeting of the caveolae, [ 102b ] and modification with albumin allowed for the uptake of NPs via caveolae. [ 104 ] Nanoparticle‐stabilized capsules (NPSC) consisting of fatty acid cores coated with gold NPs with a final diameter of ≈150 nm are another type of NPs that can be internalized by caveolae. [ 100a ] NPSCs were taken up by the cells through a cholesterol‐dependent fusion‐like process that was inhibited by M‐CD.…”

Chemistry of Advanced Nanomedicines in Cancer Cell Metabolism Regulation

“…[ 29 ] A recent follow‐up study by these scientists has also achieved brain delivery of the two agents for glioma treatment. [ 30 ]…”

“…[29] A recent followup study by these scientists has also achieved brain delivery of the two agents for glioma treatment. [30] However, as normal cells also rely on OXPHOS for ATP production, this combined approach may inevitably lead to side effect to normal tissues. To overcome this limitation, Gu et al has designed a mitochondria and nucleus dual-targeting nanosys-tem to enable tumor-specific energy depletion for eradication of liver metastasis (Figure 9).…”

Benefits of Nanomedicine for Therapeutic Intervention in Malignant Diseases

“…For example, a novel glioma-targeted nano-system with improved bioavailability was based on energy restriction therapy using menthol-modified albumin as carrier for the co-delivery of albendazole (Abz) and nano-silver on nude mice orthotopic glioma model (inoculated in the caudatoputamen). This study published in 2019 has been proven to suppress tumor growth without adverse effects [70].…”