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

Abstract

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.