Cyclodextrin-Capped Mesoporous Silica-Based Nanomaterials for pH-Responsive Targeted Theranostics of Glioblastoma Multiforme

Purpose/Objectives: Mesoporous silica nanoparticles (MSN) exhibit highly beneficial features for devising efficient nanosystems for applications in targeted cancer theranostics. Our research focuses on developing multifunctionalized and multifunctional MSN-based nanotherapeutics. Materials/Methods: The surface of MSN is functionalized with suitable biomolecules for effective targeting of brain cancer (Glioblastoma multiforme, GBM). Further surface functionalization is performed to endow the materials with linkers that are cleavable in a weakly acidic environment. This attribute is desirable to enhance the specificity of drug delivery to cancer through favorable drug release in the weakly acidic environment of tumor tissues. The anticancer drug paclitaxel is loaded in the mesopores of MSN and its retention is ensured by the acidification-cleavable linkers. Results: The release kinetics of cargo molecules is monitored and the enhanced drug release in the weakly acidic environment is observed. Furthermore, MSNs containing Gadolinium-based contrast agents were developed for enabling GBM-targeted magnetic resonance imaging (MRI) of tumor tissues. The toxicity of the materials and their cell uptake was demonstrated against GBM cells in vitro, in addition to the determination of their capabilities for tumor-targeted MRI. Conclusions: The research results evidence promising characteristics of the developed MSNs for applications in targeted treatment and magnetic resonance imaging of tumor tissues.This research was supported by the Science Fund of the Republic of Serbia, PROMIS, #6060755 (PRECAST