Improved delivery of magnetic nanoparticles with chemotherapy cancer treatment

Petryk, Alicia A.; Giustini, Andrew J.; Gottesman, Rachel E.; Hoopes, P. Jack

doi:10.1117/12.2007308

Cited by 5 publications

(6 citation statements)

References 6 publications

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“…Thus, the above conditions for the AMF, duration of MHT, and injection dose of Resovist ® appear to have been appropriate for the purpose of this study. Petryk et al reported that intraperitoneal administration of CDDP at a dose of 5 mg/kg body weight improved the delivery of MNPs to tumors in C3H mice inoculated intradermally with MTG-B cells 5) and it helped to enhance the therapeutic effect of MHT 3) . Thus, we also injected CDDP into mice intraperitoneally at a single dose of 5 mg/kg body weight according to their protocol.…”

Section: Therapeutic Effectmentioning

confidence: 99%

“…This feature of tumor tissues is called the "enhanced permeability and retention (EPR) effect" 18) . In order to develop the EPR effect, it is important to alter the tumor vascular barrier, to increase local blood flow, and to reduce tumor interstitial fluid pressure 5) .…”

Section: Therapeutic Effectmentioning

confidence: 99%

“…It has been reported that apoptosis induced by Taxane decompresses blood vessels and decreases tumor interstitial fluid pressure 19) , which could enhance the EPR effect 5) . It has also been reported that CDDP induces apoptosis of cancer cells in a dose-dependent manner, and hyperthermia enhances CDDP-induced apoptosis 20) .…”

Section: Therapeutic Effectmentioning

confidence: 99%

“…This process induces cell apoptosis, necrosis, and other cell-cycle based mechanisms 3,4) . It has been reported that a combination of chemotherapy with use of CDDP and hyperthermia produces beneficial results and synergistically enhances the effectiveness of CDDP and hyperthermia 3,5) . Magnetic hyperthermia treatment (MHT) is an attractive cancer treatment, utilizing the temperature rise of MNPs under an alternating magnetic field (AMF).…”

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confidence: 99%

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Magnetic Particle Imaging for Quantitative Evaluation of Tumor Response to Magnetic Hyperthermia Treatment Combined with Chemotherapy Using Cisplatin

Ohki¹,

Tanoue²,

Kobayashi³

et al. 2017

Thermal Med.

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This study was undertaken to evaluate the tumor response to magnetic hyperthermia treatment (MHT) combined with cisplatin (MHT ＋CDDP ) using magnetic particle imaging (MPI). Colon-26 cells were implanted into the backs of mice. When the tumor volume exceeded approximately 100 mm 3 , the mice were divided into control, MHT, CDDP, and MHT＋CDDP groups. In the CDDP and MHT＋CDDP groups, CDDP (5 mg/kg) was injected intraperitoneally. In the MHT＋CDDP group, magnetic nanoparticles ［250 mM (14.0 mg Fe/mL) Resovist ® ］ were directly injected into the tumor one hour after CDDP administration, and MHT was performed for 20 min using an alternating magnetic field. In the MHT group, only MHT was performed after the injection of Resovist ® . In the MHT＋CDDP and MHT groups, MPI images were obtained using our MPI scanner immediately before, immediately after, and 3, 7, and 14 days after MHT. After the MPI studies, we drew a region of interest (ROI) on the tumor in the MPI image and calculated the average and maximum MPI values and the number of pixels within the ROI. In all groups, the relative tumor volume growth (RTVG) was calculated from (V-V 0 ) /V0, where V 0 and V were the tumor volumes immediately before and after treatment, respectively. The RTVG value in the MHT＋CDDP group was significantly lower than that in the MHT group 3 to 14 days after MHT. It was also significantly lower than that in the CDDP group at 4 to 11 days except at 6 and 9 days after treatment. The average and maximum MPI values normalized by those immediately before MHT in the MHT＋CDDP group were significantly higher than those in the MHT group 3 days after MHT. Our results suggested that MPI is useful for quantitatively evaluating tumor response to MHT combined with chemotherapy. magnetic particle imaging, magnetic hyperthermia treatment, magnetic nanoparticles, cisplatin, tumor response

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Section: Therapeutic Effectmentioning

confidence: 99%

Section: Therapeutic Effectmentioning

confidence: 99%

Section: Therapeutic Effectmentioning

confidence: 99%

mentioning

confidence: 99%

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Magnetic Particle Imaging for Quantitative Evaluation of Tumor Response to Magnetic Hyperthermia Treatment Combined with Chemotherapy Using Cisplatin

Ohki¹,

Tanoue²,

Kobayashi³

et al. 2017

Thermal Med.

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“…Cisplatinum pre-treatment has been shown to increase iron oxide nanoparticle deposition intratumorally in a mouse model. 6 Further studies include dose modulation, timing and chemotherapy selection in order to understand how mNP delivery can be effectively integrated with conventional chemotherapy.…”

Section: ) Tumor Modification and Vascular For Nanoparticle Uptake Imentioning

confidence: 99%

Imaging and modification of the tumor vascular barrier for improvement in magnetic nanoparticle uptake and hyperthermia treatment efficacy

et al. 2013

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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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Mitigation of eddy current heating during magnetic nanoparticle hyperthermia therapy

Stigliano

Shubitidze

Petryk

et al. 2016

International Journal of Hyperthermia

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Magnetic nanoparticle hyperthermia therapy is a promising technology for cancer treatment. The technique involves delivering magnetic nanoparticles (MNPs) into tumors, then activating the MNPs using an alternating magnetic field (AMF). The AMF generating system produces not only a magnetic field, but also an electric field. The electric field penetrates normal tissue and induces eddy currents, which result in unwanted heating of normal tissues. The magnitude of the eddy current depends, in part, on the AMF source and the size of the tissue exposed to the field. The majority of in vivo MNP hyperthermia therapy studies have been performed in small animals, which, due to the spatial distribution of the AMF relative to the size of the animals, do not reveal the potential toxicity of eddy current heating in larger tissues. This limitation has posed a nontrivial challenge for researchers who have attempted to scale up from a small animal model to clinically relevant volumes of tissue. For example, the efficacy limiting nature of eddy current heating has been observed in a recent clinical trial, where patient discomfort was reported. Until now, much of the literature regarding increasing the efficacy of MNP hyperthermia therapy has focused on increasing MNP specific absorption rate or increasing the concentration of MNPs in the tumor; i.e. - improving efficacy at what is thought to be the maximum safe field strength and frequency. There has been a relative dearth of studies focused on decreasing the maximum temperature resulting from eddy current heating, to increase therapeutic ratio. This paper presents two simple and clinically applicable techniques for decreasing maximum temperature induced by eddy currents. Computational and experimental results are presented to understand the underlying physics of eddy currents induced in conducting, biological tissues and to leverage these insights for the mitigation of eddy current heating during MNP hyperthermia therapy. Phantom studies show that these techniques, termed the displacement and motion techniques, reduce maximum temperature due to eddy currents by 74% and 19% in simulation, and by 77% and 33% experimentally. Further study is required to optimize these methods for particular scenarios; however, these results suggest larger volumes of tissue could be treated, and/or higher field strengths and frequencies could be used to attain increased MNP heating, when these eddy current mitigation techniques are employed.

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Improved delivery of magnetic nanoparticles with chemotherapy cancer treatment

Cited by 5 publications

References 6 publications

Magnetic Particle Imaging for Quantitative Evaluation of Tumor Response to Magnetic Hyperthermia Treatment Combined with Chemotherapy Using Cisplatin

Magnetic Particle Imaging for Quantitative Evaluation of Tumor Response to Magnetic Hyperthermia Treatment Combined with Chemotherapy Using Cisplatin

Imaging and modification of the tumor vascular barrier for improvement in magnetic nanoparticle uptake and hyperthermia treatment efficacy

Mitigation of eddy current heating during magnetic nanoparticle hyperthermia therapy

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