Polyethylene glycol-coated porous magnetic nanoparticles for targeted delivery of chemotherapeutics under magnetic hyperthermia condition

Purpose: Although magnetite nanoparticles (MNPs) are promising agents for hyperthermia therapy, insufficient drug encapsulation efficacies inhibit their application as nanocarriers in the targeted drug delivery systems. In this study, porous magnetite nanoparticles (PMNPs) were synthesized and coated with a thermosensitive polymeric shell to obtain a synergistic effect of hyperthermia and chemotherapy. Materials and methods: PMNPs were produced using cetyltrimethyl ammonium bromide template and then coated by a polyethylene glycol layer with molecular weight of 1500Da (PEG1500) and phase transition temperature of 48 +/- 2 degrees C to endow a thermosensitive behavior. The profile of drug release from the nanostructure was studied at various hyperthermia conditions generated by waterbath, magnetic resonance-guided focused ultrasound (MRgFUS), and alternating magnetic field (AMF). The in vitro cytotoxicity and hyperthermia efficacy of the doxorubicin-loaded nanoparticles (DOX-PEG1500-PMNPs) were assessed using human lung adenocarcinoma (A549) cells. Results: Heat treatment of DOX-PEG1500-PMNPs containing 235 +/- 26 mg.g(-1) DOX at 48 degrees C by waterbath, MRgFUS, and AMF, respectively led to 71 +/- 4%, 48 +/- 3%, and 74 +/- 5% drug release. Hyperthermia treatment of the A549 cells using DOX-PEG1500-PMNPs led to 77% decrease in the cell viability due to the synergistic effects of magnetic hyperthermia and chemotherapy. Conclusion: The large pores generated in the PMNPs structure could provide a sufficient space for encapsulation of the chemotherapeutics as well as fast drug encapsulation and release kinetics, which together with thermosensitive characteristics of the PEG1500 shell, make DOX-PEG1500-PMNPs promising adjuvants to the magnetic hyperthermia modality.