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The predicted success of nanoparticle based cancer therapy is due in part to the presence of the inherent
leakiness of the tumor vascular barrier, the so called enhanced permeability and retention (EPR) effect. Although the
EPR effect is present in varying degrees in many tumors, it has not resulted in the consistent level of nanoparticle-tumor
uptake enhancement that was initially predicted. Magnetic/iron oxide nanoparticles (mNPs) have many positive
qualities, including their inert/nontoxic nature, the ability to be produced in various sizes, the ability to be activated by a
deeply penetrating and nontoxic magnetic field resulting in cell-specific cytotoxic heating, and the ability to be
successfully coated with a wide variety of functional coatings. However, at this time, the delivery of adequate numbers
of nanoparticles to the tumor site via systemic administration remains challenging. Ionizing radiation, cisplatinum
chemotherapy, external static magnetic fields and vascular disrupting agents are being used to modify the tumor
environment/vasculature barrier to improve mNP uptake in tumors and subsequently tumor treatment. Preliminary
studies suggest use of these modalities, individually, can result in mNP uptake improvements in the 3-10 fold range.
Ongoing studies show promise of even greater tumor uptake enhancement when these methods are combined. The level
and location of mNP/Fe in blood and normal/tumor tissue is assessed via histopathological methods (confocal, light and
electron microscopy, histochemical iron staining, fluorescent labeling, TEM) and ICP-MS. In order to accurately plan
and assess mNP-based therapies in clinical patients, a noninvasive and quantitative imaging technique for the assessment
of mNP uptake and biodistribution will be necessary. To address this issue, we examined the use of computed
tomography (CT), magnetic resonance imaging (MRI), and Sweep Imaging With Fourier Transformation (SWIFT), an
MRI technique which provides a positive iron contrast enhancement and a reduced signal to noise ratio, for effective
observation and quantification of Fe/mNP concentrations in the clinical setting.
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