Improved Drug Targeting to Liver Tumors After Intra-arterial Delivery Using Superparamagnetic Iron Oxide and Iodized Oil

Lee, In Joon; Ahn, Cheol Hee; Joon, Eui; Chung, In Jae; Chung, Jin Wook; Kim, Young Il

doi:10.1097/rli.0b013e31829c13ef

Cited by 19 publications

(21 citation statements)

References 34 publications

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“…The VX2 carcinoma strain was maintained in the right hind limb of a carrier rabbit by deep intramuscular injection throughout the study. [25–28] Through a midline abdominal incision, the left lobe of the liver was exposed, and a small piece of tumor (1 mm 3 ) obtained from the hind limb tumor was directly implanted into the subcapsular liver parenchyma using a needle. [25–28]…”

Section: Methodsmentioning

confidence: 99%

Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer

et al. 2016

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A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death.

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Section: Methodsmentioning

confidence: 99%

Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer

et al. 2016

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“…Doxorubicin was loaded on the surface of Resovist via an ionic interaction as previously described [[13]]. Resovist was loaded with doxorubicin through ionic interactions between anionically charged carboxydextran coating layer of Resovist and positively charged amino groups of doxorubicin.…”

Section: Methodsmentioning

confidence: 99%

The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

Jeon

Ahn

Kim

et al. 2014

J Exp Clin Cancer Res

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BackgroundLocal hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model.Materials and methodsHCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7–8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured.Bioluminescence imagings (BLIs) were performed before treatment and at 3, 7, and 14 days after treatment to measure the tumoral activities. The relative signal intensity (RSI) of each tumor was calculated by dividing the BLI signal at each time point by the value measured before treatment. At day 14 post-treatment, all tumor tissues were harvested to assess the apoptosis rates by pathological examination.ResultsThe rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively.ConclusionsThe intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model.

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“…Nanoparticles have gained an increasing importance as promising new tools for drug targeting, hyperthermia and imaging. [6][7][8][9][10][11] Especially, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs), which have been in clinical…”

Section: Introductionmentioning

confidence: 99%

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

Poller¹,

Zaloga²,

Schreiber³

et al. 2017

IJN

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Superparamagnetic iron oxide nanoparticles (SPIONs) are promising tools for the treatment of different diseases. Their magnetic properties enable therapies involving magnetic drug targeting (MDT), hyperthermia or imaging. Depending on the intended treatment, specific characteristics of SPIONs are required. While particles used for imaging should circulate for extended periods of time in the vascular system, SPIONs intended for MDT or hyperthermia should be accumulated in the target area to come into close proximity of, or to be incorporated into, specific tumor cells. In this study, we determined the impact of several accurately characterized SPION types varying in size, zeta potential and surface coating on various human breast cancer cell lines and endothelial cells to identify the most suitable particle for future breast cancer therapy. We analyzed cellular SPION uptake, magnetic properties, cell proliferation and toxicity using atomic emission spectroscopy, magnetic susceptometry, flow cytometry and microscopy. The results demonstrated that treatment with dextran-coated SPIONs (SPION Dex ) and lauric acid-coated SPIONs (SPION LA ) with an additional protein corona formed by human serum albumin (SPION LA-HSA ) resulted in very moderate particle uptake and low cytotoxicity, whereas SPION LA had in part much stronger effects on cellular uptake and cellular toxicity. In summary, our data show significant dose-dependent and particle type-related response differences between various breast cancer and endothelial cells, indicating the utility of these particle types for distinct medical applications.

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Improved Drug Targeting to Liver Tumors After Intra-arterial Delivery Using Superparamagnetic Iron Oxide and Iodized Oil

Abstract: The drug-delivery system developed using SPIO and IO can result in better drug targeting when it is used for IA delivery to liver cancer. The results of this study warrant further investigation of this potential clinical treatment of advanced liver cancer.

Cited by 19 publications

References 34 publications

Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer

Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer

The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

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