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.