Mesoporous Silica Nanoparticles for pH-Responsive Delivery of Iridium Metallotherapeutics and Treatment of Glioblastoma Multiforme

Abstract

Using nanoparticles for controlled drug delivery to cancer, in response to its weakly acidic environment, represents a promising approach toward increasing the effectiveness and reducing the adverse effects of cancer therapy. Hence, the aim of this study is to construct novel mesoporous silica nanoparticle (MSN)-based acidification-responsive drug delivery systems for targeted cancer therapy. Herein, the surface of MSN is covalently functionalized with Ir(III)-based complex through a pH-cleavable hydrazone-based linker and characterized by nitrogen sorption, SEM, FTIR, EDS, TGA, DSC, DLS, and zeta potential measurements. Enhanced release of Ir(III)-complexes is evidenced by UV/VIS spectroscopy at the weakly acidic environments (pH 5 and pH 6) in comparison to the release at physiological conditions. The in vitro toxicity of the prepared materials is tested on healthy MRC-5 cells while their potential for the efficient treatment of glioblastoma multiforme is demonstrated on the U251 cell line.