Crown ether triad modified core–shell magnetic mesoporous silica nanocarrier for pH-responsive drug delivery and magnetic hyperthermia applications

Abstract

The fabrication of drug carriers, which are desirable for chemotherapy and thermal therapy, is considered to be an attractive approach to improving the efficacy of cancer therapy and to reducing the adverse side effects. In this study, we fabricated a crown ether triad (CET) unit modified core–shell magnetic mesoporous silica (FeNP@SiOH@CET) nanocarrier system for pH-responsive drug delivery and magnetic hyperthermia applications. The CET units were installed onto the FeNP@SiOH NPs through pH-responsive, metal–ligand complexation-based host–guest interactions. The surface modified CET gating units can effectively protect the encapsulated drugs (Dox) inside the mesopores of the FeNP@SiOH@CET NP system under physiological pH conditions and show a pH-responsive release performance under acidic pH environments in the presence of an alternating magnetic field (AMF). The MTT assay and intracellular uptake results evidenced that the synthesized FeNP@SiOH@CET NPs are biocompatible and can efficiently be taken up by MDA-MB-231 cells. Furthermore, the FeNP@SiOH@CET NPs exhibit superparamagnetic behavior with a magnetic saturation value of M_s = 60.2 emu g⁻¹. In addition, the magnetic hyperthermia experiment supports that the FeNP@SiOH@CET NPs show fast and efficient temperature increases, and reach hyperthermia temperature (45 °C), within a short duration (∼4 min) in the presence of an applied magnetic field, which could be an appropriate temperature for local hyperthermia treatment in cancer therapy. Thus, the fabricated FeNP@SiOH@CET system can serve as a pH-responsive drug carrier as well as a hyperthermia agent. Owing to the synergistic effect of the FeNP@SiOH@CET NPs, they could be used for chemotherapy combined with magnetic hyperthermia-based thermal therapy applications in emerging cancer therapy.