Magnetic and pH sensitive drug delivery system through NCA chemistry for tumor targeting
For the purpose of tumor-specific drug delivery applications, a magnetic and pH dually responsive nano-carrier with a multilayer core–shell architecture was prepared from amine-functionalized Fe3O4@SiO2 through the surface-initiated ring opening polymerization of benzyl-L-aspartate N-carboxyanhydride, and then coated with α-methoxy poly(ethylene glycol) (mPEG) via a pH-sensitive benzoic–imine bond. In order to control the layer thickness of poly(benzyl-L-aspartate) (PBLA), a surface passivation agent was applied to modulate the amino density of the functionalized Fe3O4@SiO2 initiator. In this system, the Fe3O4@SiO2 nanoparticles function as a superparamagnetic core used to target the drug loaded nanocarriers to the pathological site. Meanwhile, the mPEG and PBLA segments serve as a pH-sheddable hydrophilic corona and a hydrophobic middle layer used to load the drug via hydrophobic interactions. The obtained materials were characterized by FT-IR, 1H NMR, DLS, zeta-potential, TEM, TGA and hysteresis loop analysis. Furthermore, the loading and release behavior of doxorubicin on the nanocarrier was investigated and it was shown that the drug loaded nanoparticle was relatively stable under physiological conditions and quickly released in response to acidity due to the shedding of mPEG shells through the pH-cleavage of intermediate benzoic–imine bonds. This pH and magnetic responsive nanoparticle has appeared highly promising for the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy.