Model drug-loaded mesoporous silica nanoparticles (MSNs) that are responsive to the pH rather than the redox changes normally related to glutathione (GSH) are prepared using surfactant-free MSNs as precursor. The nanoparticles are successfully shown to serve as GSH-triggered release vehicles for the guest molecules. Unlike the generally known GSH-based redox-triggered drug release action, a non-redox, ionic process associated with GSH and GSH-induced pH change enables the MSNs to release their guest molecules.