Synthesis, Characterization and In Vitro Study of New Magnetic Nanocarrier With pH‐Responsive Shell for Delivery of Methotrexate to Cancer Cells

ABSTRACT A pH‐responsive nanocarrier was prepared based on iron oxide nanoparticles successively coated with 3‐aminopropyltriethoxysilane (APTES) and methoxy poly(ethylene glycol) (mPEG) chains for intracellular delivery of methotrexate to the breast cancer cell. In this system, poly(ethylene glycol) layers are attached to the surface through pH‐sensitive benzoic‐imine bonds and serve as a pH‐sheddable hydrophilic shell. The magnetic nanocarrier was characterized by Fourier transform infrared spectroscopy, thermogravimetric analyzer, X‐ray diffractometer, transmission electron microscopy, vibrating sample magnetometer, dynamic light scattering, and zeta potential. Methotrexate was efficiently loaded into the nanoparticles with high encapsulation efficiency (75.5%) and then in vitro release analyses revealed pH‐dependent behavior. The cleavage of the benzoic–imine linkage leads to the removal of polyethylene glycol chains and subsequent release of the methotrexate at cancer tissues. Moreover, the developed formulation exhibited high toxicity toward MCF‐7 cells and also resulted in an increased rate of apoptotic MCF‐7 cells. Conclusively, the modified nanoparticles show a promising potential for delivery of anticancer drug molecules in clinical applications.