After exposure of tumor-bearing organs to AMF, the induced heat t

After exposure of tumor-bearing organs to AMF, the induced heat that raises the tissue temperature to approximately 41–47°C is known to alter the function

of many structural and enzymatic proteins within cells, which in turn arrests cell growth and differentiation and eventually induces apoptosis [6,7]. This particle-induced magnetic heating can be controlled by accurate and localized delivery of the MNPs to the target lesions, and has been under several clinical trials [8]. Additionally, MNPs have been investigated as drug delivery systems to improve the efficacy of drugs. The loading of drugs to MNPs can be achieved either by conjugating the therapeutic agents onto the surface of the MNPs or by co-encapsulating the drug molecules along with MNPs within the coating material envelope

[9]. Once at the target site, MNPs can stimulate drug uptake within cancer cells by locally providing MK-8931 price high extracellular concentrations of the drug or by direct action on the permeability of cell membranes [10]. Most of MNPs are not approved for use in humans because their safety and toxicity have not been clearly documented. However, ferucarbotran (Resovist; Bayer Schering Pharma AG, Leverkusen, Germany) is a clinically-approved superparamagnetic iron oxide nanoparticle that has been developed for contrast-enhanced MRI of the liver [11]. Local hyperthermia of tumor tissue in conjunction with chemotherapy has been demonstrated to significantly enhance antitumor efficacy [12]. Here, we designed a complex made with both Resovist, CYTH4 an MNP approved for clinical use in humans, and doxorubicin to combine the magnetic control of heating and drug delivery into one treatment. We expected that this complex would enhance the synergistic efficacy and yield substantial promise for a highly efficient therapeutic strategy in HCC. The in vivo antitumor effect was evaluated by bioluminescence imaging (BLI),

which measures the luciferase-expressing tumor cells’ activity, throughout the follow-up period. Materials and methods Preparation of the Resovist/doxorubicin complex 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. Predetermined amount of doxorubicin (0.2 mg, Adriamycin; Ildong Pharmaceutical, Seoul, Republic of Korea) was selleck products dissolved in 4 mL deionized water, and the aqueous solution was transferred to a 250-mL round-bottom flask. Diluted (1.38 Fe mg/mL) Resovist in 4 mL deionized water was added dropwise using a syringe pump at a rate of 0.1 mL/min, and the reaction mixture was vigorously stirred for 8 hours. Loading efficiency of doxorubicin was 100% and ultraviolet–visible spectroscopy at 480 nm confirmed that there was not any doxorubicin left in the aqueous solution.

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