Intelligent Drug Delivery System Based on Mesoporous Silica Nanoparticles Coated with an Ultra-pH-Sensitive Gatekeeper and Poly(ethylene glycol)

Mesoporous silica nanoparticles (MSNs) exhibit significant advantages for efficient drug/gene delivery but it is hard for simple MSNs to deliver the loaded drug to the target sites of disease. Considering that there are some well-known pH differences in the body, it is a useful strategy to modify the exterior surface of MSNs with stimuli-responsive gatekeepers to realize open–close transformation of their mesopores. In this work, multifunctional pH-sensitive MSNs were designed with mixed polymeric coatings, that is, poly­(ethylene glycol) (PEG) as a dispersity-enhancer and poly­(2-(pentamethyleneimino)­ethyl methacrylate) (PPEMA) as an ultra-pH-sensitive gatekeeper. Enhanced dispersity, high drug loading capacity, long-circulation time, pH-triggered targeting, and better cellular uptake of the multifunctional MSNs make them potential candidates for pH-sensitive drug delivery such as tumor therapy