Brain-Targeted Delivery and Redox-Responsive Release of Protein Therapeutics via GSH-Sensitive SiO₂ Nanoparticles

Abstract

This study In this study,  we have presented an idea of developing and evaluating a glutathione (GSH) responsive, aptamer functionalized silica nanoparticle system (FITC-BSA@Apt-SiO₂) for targeted protein delivery to glioma tumor. Disulfide-containing organ silanes (BTEPDS) were introduced into the nanoparticles synthesized via reverse microemulsion method so as to allow their degradation under GSH tumor mimicking conditions through reductive cleavage. FITC-BSA was successfully encapsulated inside the PLGA microspheres, and the microspheres were surface modified with the AS1411 aptamer for tumor targeting capability. In addition, the spherical morphology of NPs was confirmed by transmission electron microscopy (TEM) with a size distribution of 43.5 – 61.5 nm and the degradation behavior were investigated by TEM, as well as cumulative protein release determined by a BCA assay, in which both methods indicated large GSH-dependent breakdown after 24 hours. Furthermore, in vivo fluorescence imaging in glioma bearing mice proved effective blood-brain barrier penetration and accumulation at the tumor site observed for FITC-BSA@AptSiO₂ in comparison to non-targeted controls. Examination of the excellent biocompatibility and localized action has been confirmed through hemolysis and mouse tail bleeding assays to avoid systemic toxicity. Our findings confirm that FITC-BSA@Apt-SiO₂ is a smart responsive nanocarrier system for tumor targeted delivery of therapeutic protein especially applied in treatments of glioma, which requires crossing the BBB and delivering its contents intracellularly upon demand.