Design of thermosensitive polymer‐coated magnetic mesoporous silica nanocomposites with a core‐shell‐shell structure as a magnetic/temperature dual‐responsive drug delivery vehicle

Abstract A stimuli‐responsive nanocomposite with a core‐shell‐shell structure consisting of iron oxide (Fe 3 O 4 ) 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)@mSiO 2 @Fe 3 O 4 ) were characterized by XRD, FTIR, and TEM analyses. Also, the heating ability of mesoporous silica‐coated Fe 3 O 4 nanoparticles, and P(NIPAAm‐co‐AAc)@mSiO 2 @Fe 3 O 4 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)@mSiO 2 @Fe 3 O 4 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.