Functionalized Mesoporous Silica@Mercuric Oxide Core–Shell Nanoparticles Loaded with Temozolomide for Targeted Treatment of Glioma

In this research, we synthesized mesoporous silica@mercury oxide nanoparticles featuring a core-shell structure (MSM) for the nasal delivery of Temozolomide (TMZ) to achieve targeted treatment of glioma. Nasal administration can bypass the first-pass metabolism in the liver. Through the olfactory nerve, mesoporous silica@mercury oxide-Temozolomide-serum-folic acid (MSMTSF) travels directly to the brain. The use of folic-acid-functionalized plasma active components allows TMZ to be delivered specifically to the glioma lesion site. At the lesion site, HgO can promote the production of ROS, causing excessive oxidative stress, which, in turn, impairs mitochondrial function and promotes apoptosis. Simultaneously, TMZ can act synergistically to promote the apoptosis of tumor cells and exert antitumor effects. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed that the particle size of MSM was approximately 126.57 ± 5.33 nm. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) authenticated that TMZ existed in an amorphous state within the mesoporous channels. The results of the in vitro release experiment indicated that MSMTSF could significantly enhance the solubility of TMZ and exhibited a sustained-release effect. Cell uptake experiments and in vivo imaging validated the superior targeting ability of MSMTSF. The fluorescence of DCFH-DA, flow cytometry, cellular immunofluorescence, Western blot, and in vivo animal experiments jointly demonstrated that MSMTSF could induce excessive oxidative stress, impair mitochondrial function, and synergize with TMZ to promote the apoptosis of C6 cells. These results suggest that MSMTSF may be a promising nanosystem for the targeted treatment of glioma.