A stimuli-responsive nanocomposite with a core-shell-shell structure consisting of iron oxide (Fe3O4) nanoparticles as core, mesoporous silica as middle shell, and poly(N-isopropyl acrylamide-co-acrylic acid) (P[NIPAAm-co-AAc]) as an exterior shell with thermo-responsivity properties was synthesized to be used as a magnetic/temperature responsive drug delivery system. The structure, morphology, and size of P(NIPAAm-co-AAc)-coated mesoporous silica embedded magnetite nanoparticles (P(NIPAAm-co-AAc)@mSiO2@Fe3O4) were characterized by XRD, FTIR, and TEM analyses. Also, the heating ability of mesoporous silica-coated Fe3O4 nanoparticles, and P(NIPAAm-co-AAc)@mSiO2@Fe3O4 nanocomposites was investigated under the exposure of an alternating magnetic field (AMF). The results indicated that the prepared nanocomposites could generate enough heat for hyperthermia applications. Moreover, the magnetic/temperature-responsive drug release behavior of P(NIPAAm-co-AAc)@mSiO2@Fe3O4 nanocomposites loaded with fluorouracil (5-FU) was studied under the exposure of the AMF (frequency = 120 kHz, and amplitude = 22 kA m−1), as well as two different temperatures (37°C and 45°C). The results showed that only 7.8% of the drug could be released after 20 h at 37°C (below the LCST of the copolymer). In contrast, by increasing the temperature of release medium up to 45°C (above the LCST of the copolymer), the amount of released drug was increased up to 47%. Moreover, by exposing the prepared nanocomposite to a safe AMF, a burst release of drug was observed, indicating the excellent responsivity of the carrier to an external magnetic field. These results proved that the obtained nanocomposite has a great performance to be used as a magnetic/temperature-sensitive drug carrier for advanced drug delivery applications.
