Paclitaxel-Ang-2-functionalized bionic mesoporous selenium nanoparticles for targeted therapy of glioma

Abstract

Glioma, the most prevalent primary intracranial tumor, presents significant clinical treatment challenges due to its high invasiveness and therapeutic resistance. Therefore, the development of a targeted therapeutic agent that is both highly effective and low in toxicity is crucial. In this research, we aimed to design a bionic mesoporous selenium nanoparticle (ACMLMSeP) functionalized with paclitaxel and Ang-2 for nasal administration as a targeted treatment approach for glioma. Nasal administration facilitates direct delivery of drugs to the brain through the olfactory nerve, thereby circumventing the protective mechanisms of the blood-brain barrier. Mesoporous selenium (MSe) significantly enhances the loading capacity for insoluble drugs while improving their water solubility. The functionalization of MSe enables slow drug release and facilitates targeted drug accumulation. Moreover, accumulated nano-selenium promotes reactive oxygen species (ROS) production, induces autophagy, and synergizes with drugs to accelerate apoptosis in tumor cells. Analysis using Transmission Electron Microscopy (TEM) images and Dynamic Light Scattering (DLS) indicated that ACMLMSe has an average particle size of roughly 135 nm. Results from in vitro release assessments indicated that the ACMLMSeP sustained the release of the drug, reaching a total release rate of 74.96 ± 2.34 % within 24 h. Cellular uptake studies and in vivo imaging showed the strong targeting capabilities of the ACMLMSeP nanoparticles. Furthermore, the results obtained from the MTT assays, flow cytometry analysis, immunofluorescence staining, and in vivo antitumor evaluations collectively revealed that ACMLMSeP effectively inhibited proliferation while promoting apoptosis in C6 cells. In summary, these experimental findings clearly suggest that ACMLMSeP may serve as a promising biomimetic nanosystem for the targeted treatment of brain glioma.