Hyperthermia evaluation and drug/protein-controlled release using alternating magnetic field stimuli-responsive Mn-Zn ferrite composite particles

Drug delivery particles in which the release of biomolecules is triggered by a magnetic simulant have attracted much attention and may have great potential in the fields of cancer therapy and tissue regenerative medicine. In this study, we have prepared magnetic Mn-Zn ferrite ((Mn,Zn)Fe2O4) (MZF) nanoparticles coated with chitosan-g-N-isopropylacrylamide (Chi-g-NIPAAm) polymer (MZF@Chi-g-NIPAAm) to deliver the anticancer drug (Doxorubicin, DOX) and bioactive proteins (Bone morphogenic protein (BMP-2)-immobilized bovine serum albumin (BSA)) (P//MZF@Chi-g-NIPAAm) and be used as chemo-hyperthermia and vector delivering biomolecules. For these purposes, we first show that the as-prepared MZF@Chi-g-NIPAAm particles exhibit super paramagnetic behavior and under certain conditions, they can act as a heat source with a specific absorption rate (SAR) of 34.88 W g(-1). Under acidic conditions and in the presence of AMF, the fast release of DOX was seen at around 58.9% within 20 min. In vitro evaluations indicated that concurrent thermo-chemotherapy treatment by DOX-MZF@Chi-g-NIPAAm using AMF had a better antitumor effect, compared with those using either DOX or DOX-MZF@Chi-g-NIPAAm without AMF (89.02% of cells were killed as compared to 71.82% without AMF exposure). Up to 28.18% of the BSA (used as the model protein to determine the controlled release) is released from the P//MZF@Chi-g-NIPAAm particles under AMF exposure for 1 h (only 17.31% was released without AMF). These results indicated that MZF@Chi-g-NIPAAm particles could be used to achieve hyperthermia at a precise location, effectively enhancing the chemotherapy treatments, and have a promising future as drug or bioactive delivering molecules for cancer treatment and cartilage or bone regenerative applications.