Modeling the performance of magnetic nanoparticles in multimodal cancer therapy

Composite magnetic nanoparticles (MNPs) consisting of an MNP core and drug loaded polymer shell can increase the efficacy of cancer therapy by overcoming several limitations of conventional hyperthermia and chemotherapy. Multimodal therapy consisting of simultaneous hyperthermia and chemotherapy can increase therapeutic efficiency compared to individual applications of these modalities. Factors influencing power output in an alternating magnetic field (AMF) for superparamagnetic γ-Fe₂O₃ and Fe₃O ₄ iron oxide MNP were studied. The optimum MNP properties for in vivo magnetic hyperthermia were identified. For a 375 kHz AMF, 23 nm γ-Fe ₂O₃ MNP and 12 nm Fe₃O₄ MNP produce maximum heating, heat generation is dependent primarily on Ńel relaxation and is insensitive to polymer shell thickness. The heating of tumors by uniformly distributed magnetic clusters of optimized iron oxide MNP was modeled. The MNP mass required to heat tumors to hyperthermia temperatures was calculated, the Fe₃O₄ MNP concentration in the tumor required for hyperthermia was in the range of 0.12-2.2 g ml^-1 for Fe₃O₄ and 0.06-1.7 g ml^-1 for γ-Fe ₂O₃ MNP respectively. In vitro drug release from doxorubicin loaded poly-n-isopropylacrylamide coated MNP was also modeled to understand the influence of shell thickness on thermoresponsive drug release. An increase in shell thickness or decrease in temperature resulted in decreased drug release rates. The MNP mass requirements for hyperthermia closely match the requirements for chemotherapy confirming the feasibility of these particles for combined hyperthermia and drug release applications.