A magnetic, reversible pH-responsive nanogated ensemble based on Fe3O4 nanoparticles-capped mesoporous silica

Stimuli-sensitive mesoporous silica nanoparticles (MSNs)-based hybrid “gate-like” ensembles capable of performing specific programmed release mode represent a new generation delivery system in recent years. In this paper, a magnetic and reversible pH-responsive, MSNs-based nanogated ensemble was fabricated by anchoring superparamagnetic Fe3O4 nanoparticles on the pore outlet of MSNs via a reversible boronate esters linker. To achieve this, MSNs and Fe3O4 nanoparticles were first synthesized and functionalized by polyalcohol derivative and boronic acid, respectively. The successful incorporation of Fe3O4 nanoparticles onto the MSNs was confirmed by the results of XRD, TEM, XPS and N2 adsorption-desorption method. The pH-driven “gate-like” effect was studied by in vitro release of an entrapped model dexamethasone from the pore voids into the bulk solution at different pH values. The results indicated that at pH 5–8, the pores of the MSNs were effectively capped with Fe3O4 nanoparticles and the drug release was strongly inhibited. While at pH 2–4, the hydrolysis of the boroester bond took place and thus resulted in a rapid release of the entrapped drug. And by alternately changing the pH from 3 to 7, these Fe3O4 cap gate could be switched “on” and “off” and thereby released the entrapped drug in a pulsinate manner (in small portions). Additionally, this nanogated release system exhibited good magnetic property, high cell biocompatibility and cellular uptake for MC3T3-E1 cells. The present data suggest that it is possible to obtain simple and very effective pH-driven pulsinate release using these Fe3O4-capped-MSNs, and this new platform represents a promising candidate in the formulation of in vivo targeted delivery of therapeutic agents to low pH tissues, such as tumors and inflammatory sites.