Assessment of intratumor non-antibody directed iron oxide nanoparticle hyperthermia cancer therapy and antibody directed IONP uptake in murine and human cells

Hoopes, P. Jack; Tate, Jennifer A.; Ogden, Janet; Strawbridge, Rendall R.; Fiering, Steven; Petryk, Alicia A.; Cassim, Shiraz M.; Giustini, Andrew J.; Demidenko, Eugene; Ivkov, Robert; Barry, Sheila; Chinn, Paul; Foreman, Allan R.

doi:10.1117/12.812056

Cited by 10 publications

(8 citation statements)

References 17 publications

(2 reference statements)

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“…In addition to higher levels of intracellular iron, the 72 hour incubation time may have resulted in different intracellular groupings of iron as compared to samples incubated for 48 hours, although nanoparticle configurations were not characterized here 8,9 . Changes in configuration may have included aggregation or dispersion of IONPs within the cell, average distance from the nucleus, or the onset of degradation of the starch coating of the particles.…”

Section: Discussionmentioning

confidence: 97%

Iron oxide nanoparticle enhancement of radiation cytotoxicity

et al. 2013

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Iron oxide nanoparticles (IONPs) have been investigated as a promising means for inducing tumor cell-specific hyperthermia. Although the ability to generate and use nanoparticles that are biocompatible, tumor specific, and have the ability to produce adequate cytotoxic heat is very promising, significant preclinical and clinical development will be required for clinical efficacy. At this time it appears using IONP-induced hyperthermia as an adjunct to conventional cancer therapeutics, rather than as an independent treatment, will provide the initial IONP clinical treatment. Due to their high-Z characteristics, another option is to use intracellular IONPs to enhance radiation therapy without excitation with AMF (production of heat). To test this concept IONPs were added to cell culture media at a concentration of 0.2 mg Fe/mL and incubated with murine breast adenocarcinoma (MTG-B) cells for either 48 or 72 hours. Extracellular iron was then removed and all cells were irradiated at 4 Gy. Although samples incubated with IONPs for 48 hrs did not demonstrate enhanced post-irradiation cytotoxicity as compared to the non-IONP-containing cells, cells incubated with IONPs for 72 hours, which contained 40% more Fe than 48 hr incubated cells, showed a 25% decrease in clonogenic survival compared to their non-IONP-containing counterparts. These results suggest that a critical concentration of intracellular IONPs is necessary for enhancing radiation cytotoxicity.

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Section: Discussionmentioning

confidence: 97%

Iron oxide nanoparticle enhancement of radiation cytotoxicity

et al. 2013

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“…6 (MicroMod #10-00-102, starch-coated, iron oxide (Fe 3 O 4 ), saturation magnetization >76 emu/gFe, 100 nm particle diameter, 66 nm iron oxide core diameter, 15 mg Fe/mL aqueous solution).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast to previous studies, the IONPs we injected have been used for hyperthermia therapy in animal models. 6 …”

Section: Introductionmentioning

confidence: 99%

Targeting of systemically-delivered magnetic nanoparticle hyperthermia using a noninvasive, static, external magnetic field

Zulauf

Trembly

Giustini³

et al. 2013

SPIE Proceedings

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One of the greatest challenges of nanoparticle cancer therapy is the delivery of adequate numbers of nanoparticles to the tumor site. Iron oxide nanoparticles (IONPs) have many favorable qualities, including their nontoxic composition, the wide range of diameters in which they can be produced, the cell-specific cytotoxic heating that results from their absorption of energy from a nontoxic, external alternating magnetic field (AMF), and the wide variety of functional coatings that can be applied. Although IONPs can be delivered via an intra-tumoral injection to some tumors, the resulting tumor IONP distribution is generally inadequate; additionally, local tumor injections do not allow for the treatment of systemic or multifocal disease. Consequently, the ultimate success of nanoparticle based cancer therapy likely rests with successful systemic, tumor-targeted IONP delivery. In this study, we used a surface-based, bilateral, noninvasive static magnetic field gradient produced by neodymium-boron-iron magnets (80 T/m to 130 T/m in central plane between magnets), a rabbit ear model, and systemically-delivered starch-coated 100 nm magnetic (iron oxide) nanoparticles to demonstrate a spatially-defined increase in the local tissue accumulation of IONPs. In this non-tumor model, the IONPs remained within the local vascular space. It is anticipated that this technique can be used to enhance IONP delivery significantly to the tumor parenchyma/cells.

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“…(20, 21) Dextran coated nanoparticles were modeled as clustered together at the center of the lowest particle-containing control volume in the three-particle model space.…”

Section: Fem Numerical Modelsmentioning

confidence: 99%

FEM numerical model study of heating in magnetic nanoparticles

et al. 2011

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Electromagnetic heating of nanoparticles is complicated by the extremely short thermal relaxation time constants and difficulty of coupling sufficient power into the particles to achieve desired temperatures. Magnetic field heating by the hysteresis loop mechanism at frequencies between about 100 and 300 kHz has proven to be an effective mechanism in magnetic nanoparticles. Experiments at 2.45 GHz show that Fe3O4 magnetite nanoparticle dispersions in the range of 1012 to 1013 NP/mL also heat substantially at this frequency. An FEM numerical model study was undertaken to estimate the order of magnitude of volume power density, Qgen (W m−3) required to achieve significant heating in evenly dispersed and aggregated clusters of nanoparticles. The FEM models were computed using Comsol Multiphysics; consequently the models were confined to continuum formulations and did not include film nano-dimension heat transfer effects at the nanoparticle surface. As an example, the models indicate that for a single 36 nm diameter particle at an equivalent dispersion of 1013 NP/mL located within one control volume (1.0 × 10−19 m3) of a capillary vessel a power density in the neighborhood of 1017 (W m−3) is required to achieve a steady state particle temperature of 52 °C — the total power coupled to the particle is 2.44 μW. As a uniformly distributed particle cluster moves farther from the capillary the required power density decreases markedly. Finally, the tendency for particles in vivo to cluster together at separation distances much less than those of the uniform distribution further reduces the required power density.

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Assessment of intratumor non-antibody directed iron oxide nanoparticle hyperthermia cancer therapy and antibody directed IONP uptake in murine and human cells

Cited by 10 publications

References 17 publications

Iron oxide nanoparticle enhancement of radiation cytotoxicity

Iron oxide nanoparticle enhancement of radiation cytotoxicity

Targeting of systemically-delivered magnetic nanoparticle hyperthermia using a noninvasive, static, external magnetic field

FEM numerical model study of heating in magnetic nanoparticles

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