Magnetic mesoporous silica nanoparticles mediated redox and pH dual-responsive target drug delivery for combined magnetothermal therapy and chemotherapy

Abstract

A combination of multiple therapies is conducive to the treatment efficacy of cancer. Chemotherapy combined with magnetothermal therapy provides an outstanding synergy for cancer treatment. In this study, magnetic mesoporous silica nanoparticles (MMSN) were developed as a multipurpose nanoplatform for doxorubicin (DOX) delivery and magnetothermal treatment of cancer simultaneously. The MMSN were composed of Fe3O4 and mesoporous silica as core and shell. The folic acid (FA) linked chitosan (CS) was conjugated at the outlets of MMSN (MMSN-SS-FA) using disulfide bonds to avert the premature release of the drug in mesopores of MMSN, target folate receptor-overexpressed cancer cells and increase the safety and physiological stability of MMSN. The temperature of the MMSN suspension could be elevated from 37 °C to 45 °C at the concentration of 1 mg/mL under an alternating magnetic field (AMF), which exceeded the tumor ablating temperature. The in vitro drug release proved that the DOX/MMSN-SS-FA displayed the redox/pH/AMF multiple-responsive release. The cellular uptake results indicated that the MMSN-SS-FA could target folate receptor-overexpressed HeLa cells. The DOX/MSNS-SS-FA with AMF had the highest cytotoxicity at the equivalent drug concentration towards HeLa cells with a combination index (CI) of 0.276, demonstrating the synergistic treatment effect of chemotherapy and magnetic-thermal therapy. Meanwhile, the DOX/MMSN-SS-FA+AMF showed the strongest tumor inhibitory effect of 84 % on tumor growth. Therefore, the constructed MMSN-SS-FA with good biocompatibility and biosafety can act as multifunctional nano-platforms for tumor treatment.