Redox-responsive and surface protein-retractive mesoporous organosilica nanoparticles for enhanced cancer therapy

Abstract

Targeted delivery along with controlled drug release is considered crucial in development of a drug delivery system (DDS) for efficient cancer treatment. In this study, we present a novel approach to obtain such a DDS by utilizing disulfide-incorporated mesoporous organosilica nanoparticles (MONs), which were designed to minimize the surface interactions with proteins, thereby enhancing targeting and therapeutic performance. That is, after MONs were loaded with a chemodrug doxorubicin (DOX) within their inner pores, and outer surface was treated for conjugation to the glutathione-S-transferase (GST)-fused cell-specific affibody (Afb) (GST-Afb). These modified particles exhibited prompt responsiveness to the SS bond-breaking glutathione (GSH), which resulted in significant degradation of the initial particle morphology and DOX release. As reduced protein adsorption on the MON surface, their targeting ability with GSH-stimulated therapeutic activities was demonstrated in vitro by using two types of GST-Afb protein, which target human cancer cells with the specific surface membrane receptor, HER2 or EGFR. Compared with unmodified control particles, the presented results show that our system can significantly enhance cancer-therapeutic outcomes of the loaded drug, offering a promising approach of designing a more efficacious DDS.