Modeling the performance of magnetic nanoparticles in multimodal cancer therapy

Abstract

Composite magnetic nanoparticles ͑MNPs͒ 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 ͑AMF͒ for superparamagnetic ␥-Fe 2 O 3 and Fe 3 O 4 iron oxide MNP were studied. The optimum MNP properties for in vivo magnetic hyperthermia were identified. For a 375 kHz AMF, 23 nm ␥-Fe 2 O 3 MNP and 12 nm Fe 3 O 4 MNP produce maximum heating, heat generation is dependent primarily on Néel 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 Fe 3 O 4 MNP concentration in the tumor required for hyperthermia was in the range of 0.12-2.2 g ml −1 for Fe 3 O 4 and 0.06-1.7 g ml −1 for ␥-Fe 2 O 3 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.

Thermoresponsive Polymers for Biomedical Applications

“…Upon heating above the LCST, the coating shrinks and releases the active drug [149,151,152,155,156]. Purushotham also showed the possibility of using a magnetic field to heat the composite and hence release entrapped drugs form the thermoresponsive coating [150]. Work by Papaphilippou et al has involved the preparation of hybrid micelles utilizing a thermoresponsive PEGMA containing polymer and a magnetite nanoparticle core [154].…”

“…Much work has been done on the modification of inorganic particles with thermoresponsive polymers [148][149][150][151][152][153][154]. Zhang et al coated insoluble nanoparticles with PNIPAAm rendering them stable in aqueous solutions with temperature dependant solution properties and suggested uses in drug delivery and biological sensing [148].…”

Influence of dipolar interactions on hyperthermia properties of ferromagnetic particles

“…Modeling of the performance of magnetic NPs in hyperthermia has been previously reported. 9,10 However, it has not been clarified yet if an increase in the concentration of particles leads to an increase in the heating capacity, or to a decrease as recently suggested by Urtizberea et al 11 Therefore, the use of Monte Carlo ͑MC͒ simulation methods could be of valuable help to analyze the performances of ferromagnetic NPs for hyperthermia applications. Our previous results demonstrated that nanostructured Fe NPs coated with a uniform MgO epitaxial shell may act as high performance therapy vectors with similar heating power of existing materials but at much more lower doses.…”

Magnetothermoacoustics from magnetic nanoparticles by short bursting or frequency chirped alternating magnetic field: A theoretical feasibility analysis

“…It should be noticed that, the 0.8 mg/ml SPION matrix used for the model-computation is estimated to be 16 times of the safe dosing of SPION in plasma, 50 μg/ml, which corresponds to 5 mg/kg body-weight of SPION, 31,32 50 kg body weight and 5000 ml blood. By targeting SPION with a specific biomarker, it may be feasible to enhance the site-specific delivery of the SPION multiple fold of that of the plasma concentration.…”