Ultrasonic De-cross-linking of the pH- and Magneto-Responsive PHEMA/PMMA Microgel to Janus Nanoparticles: A New Synthesis Based on Grafting from/Grafting to Polymerization

Stimuli responsive Janus nanoparticles (NPs) with a two-facial structure have been used widely in biomedical applications. Among several methods to prepare these NPs, surface-initiated atom transfer radical polymerization (SI-ATRP) has received much attention due to the precise deposition of polymers on the surface of the substrate. In this study, Janus nanoparticles with asymmetric surface chemistry were prepared through a masking method in three steps involving the covalent deposition of super paramagnetic iron oxide nanoparticles (SPIONs) on the cross-linked substrate based on methotrexate (MTX)-grafted poly(2-hydroxyethyl methacrylate) (CPM), surface functionalization of unreacted sites of immobilized SPIONs with 2-bromoisobutyryl bromide (BIBB) in order to prepare the macro-initiator (Br-Fe3O4-CPM), growing poly(methyl methacrylate) (PMMA) on the surface of the macro-initiator through the SI-ATRP method. Optical microscopy was utilized to monitor the successful modification of SPIONs. Poly(methyl methacrylate)-iron oxide-poly(2-hydroxyethyl methacrylate) (PMMA-Fe3O4-PHEMA) microgel was exposed to optimum ultrasound (US) waves to prepare the PMMA-Fe3O4-PHEMA nanoparticle. Transmission electron microscopy (TEM) was used to confirm the precise deposition of polymers and the Janus structure. The MTX release of US-synthesized Janus NPs was studied in PBS at pH values of 7.4 and 5.8. The release data were analyzed using the Excel add-in DDSolver program to evaluate the kinetics of the drug release process from the nanocarrier under different pH values.