Ultrasound/redox/pH-responsive hybrid nanoparticles for triple-triggered drug delivery

We have developed a triple pH/redox/ultrasound-triggered hybrid nanocarrier system for controlled drug de-livery. This multifunctional hybrid system was synthesized as a core/shell nanoparticle consisting of mesoporous silica coated magnetic core (Fe3O4@SiO2@mSiO(2)) and pH/redox-responsive polymer layer. We synthesized lipoic acid (LA)-conjugated chitosan (CS) polymer as pH/redox-responsive polymer (CS-LA) layer of the particles. Then the synthesized ellipsoidal Fe3O4@SiO2@mSiO(2) nanoparticles were coated by CS-LA polymer. To prepare triple-responsive release system, the LA components of the CS-LA polymer layer were crosslinked by DTT. The results showed that the hybrid nanoparticles exhibited an efficient DOX release in cellular pH environment. In addition, the dual pH/redox-responsive drug release results exhibited that the hybrid nanoparticles showed an efficient and controlled drug release profile in the presence of 10 mM GSH at pH = 5.5 at 37 degrees C within 24 h. Ultrasound (US)-induced release profile of the hybrid nanoparticles showed that the DOX release behaviour was controlled effectively by US-triggered. In vitro cytotoxicity tests exhibited that DOX loaded hybrid nanoparticles provide an efficient cell death in MCF-7 cells at pH = 5.5. In our belief, these triple-triggered hybrid nano-particles have promising potential for controlled drug release and are worth doing further in vivo research.