Magnetic and pH-sensitive nanoparticles for antitumor drug delivery

A dually responsive nanocarrier with multilayer core–shell architecture was prepared based on Fe 3 O 4 @SiO 2 nanoparticles coated with mPEG-poly( l -Asparagine). Imidazole groups (pK a   ∼   6.0) were tethered to the side chains of poly( l -Asparagine) segments by aminolysis. These nanoparticles were expected to be sensitive to both magnetic field and pH environment. The obtained materials were characterized with FTIR, dynamic light scattering, ζ -potential, TEM, TGA and hysteresis loop analysis. It was found that this Fe 3 O 4 @SiO 2 –polymer complex can form nano-scale core–shell–corona trilayer particles (∼250   nm) in aqueous solution. The Fe 3 O 4 @SiO 2 , poly( l -Asparagine) and mPEG segments serve as a super-paramagnetic core, a pH-sensitive shell, and a hydrophilic corona, respectively. An antitumor agent, doxorubicin (DOX), was successfully loaded into the nanocarrier via combined actions of hydrophobic interaction and hydrogen bonding. The drug release profiles displayed a pH-dependent behavior. DOX release rate increased significantly as the ambient pH dropped from the physiological pH (7.4) to acidic (5.5). This is most likely due to protonation and a change in hydrophilicity of the imidazole groups in the poly( l -Asparagine) segments. This new approach may serve as a promising platform to formulate magnetic targeted drug delivery systems.