Pluronic@Fe3O4 nanoparticles with robust incorporation of doxorubicin by thermo-responsiveness

Abstract

Doxorubicin was physically incorporated in magnetic nanoparticles by thermo-responsive manners. Magnetic nanoparticles were prepared by oxidizing ferric ions in ammonium solution. Thiolated Pluronic was synthesized by sequential modification of terminal hydroxyl groups of Pluronic to amine groups and thiol groups. Magnetic nanoparticles composed of iron oxide were surface-modified with thiolated Pluronic at different molar ratios of iron to thiol groups. Pluronic decoration on the magnetic nanoparticles was characterized by elemental analysis and transmission electron microscopy. Elemental analysis results on carbon atoms in the magnetic nanoparticles showed that the degree of Pluronic decoration was proportional to the feed ratio of thiolated Pluronic to iron oxide. Doxorubicin was incorporated to the magnetic nanoparticles thermo-responsive manners; a mixture of hydrophobized doxorubicin and the magnetic nanoparticles was incubated at 4°C and the temperature was subsequently increased to 37°C for thermally induced structural changes of the decorated Pluronic moieties. Doxorubicin-incorporated magnetic nanoparticles showed dramatic modulations of size distributions according to temperature changes, which was dependent on the degree of Pluronic decoration. Loading efficiency of doxorubicin was significantly affected by the number of decorated Pluronic on the magnetic nanoparticles; the higher Pluronic moieties the nanoparticles had, the higher loading efficiency they showed. Release profiles of doxorubicin from the nanoparticles showed that doxorubicin was liberated from the nanoparticles in response to reducing conditions of the release medium. Anti-cancer activities of the doxorubicin-incorporated nanoparticles were determined by a MTT-based cytotoxicity assay against A549 cell lines. Compared to native doxorubicin, the doxorubicin incorporated magnetites showed attenuated cytotoxicities due to slow release of doxorubicin from the carriers. Thus, thermally induced incorporation of anti-cancer drugs can be a novel method for multifunctional magnetic nanoparticles with imaging and anti-cancer treatments.