Abstract
BackgroundBoth thermotherapy and arsenic have been shown to be active against a broad spectrum of cancers. To reduce the limitations of conventional thermotherapy, improve therapeutic anticancer activity, reduce the toxicity of arsenic on normal tissue, and increase tissue-specific delivery, we prepared a nanosized As2O3/Fe3O4 complex (Fe3O4 magnetic nanoparticles encapsulated in As2O3). We assessed the thermodynamic characteristics of this complex and validated the hyperthermia effect, when combined with magnetic fluid hyperthermia (MFH), on xenograft HeLa cells (human cervical cancer cell line) in nude mice. We also measured the effect on the expression of CD44v6, VEGF-C, and MMP-9 which were related to cancer and/or metastasis.ResultsThe nanosized As2O3/Fe3O4 particles were approximately spherical, had good dispersibility as evidenced by TEM, and an average diameter of about 50 nm. With different concentrations of the nanosized As2O3/Fe3O4 complex, the correspondingsuspension of magnetic particles could attain a steady temperature ranging from 42°C to 65°C when placed in AMF for 40 min. Thermochemotherapy with the nanosized As2O3/Fe3O4 complex showed a significant inhibitory effect on the mass (88.21%) and volume (91.57%) of xenograft cervical tumors (p < 0.05 for each measurement, compared with control). In addition, thermochemotherapy with the nanosized As2O3/Fe3O4 complex significantly inhibited the expression of CD44v6, VEGF-C, and MMP-9 mRNA (p < 0.05 for each).ConclusionAs2O3/Fe3O4 complex combined with MFH had is a promising technique for the minimally invasive elimination of solid tumors and may be have anticancerometastasic effect by inhibiting the expression of CD44v6, VEGF-C, and MMP-9.
Highlights
Both thermotherapy and arsenic have been shown to be active against a broad spectrum of cancers
Upon dispersion in 0.9% (w/v) NaCl and exposure to high frequency alternating magnetic field (AMF) for 60 min, the nanosized As2O3/Fe3O4 complexes increased the temperature of magnetic fluid (MF) from 42°C to 65°C, depending on the concentration of Fe3O4 (Figure 2), with a permanent change seen after 40 min of electromagnetic exposure
In Vivo Inhibitory Effects of the As2O3/Fe3O4 Complex and AMF exposure on Xenograft Cervical Cancer in Nude Mice Following intratumor injection of simple Fe3O4 magnetic nanoparticles or nanosized As2O3/Fe3O4 complexes, and exposure to high frequency AMF (f = 230 kHz, I = 20 A) for 30 min, almost the entire tumor got heated by the nanoparticles and the temperature of tumors rose to 44°C45°C
Summary
Both thermotherapy and arsenic have been shown to be active against a broad spectrum of cancers. To reduce the limitations of conventional thermotherapy, improve therapeutic anticancer activity, reduce the toxicity of arsenic on normal tissue, and increase tissuespecific delivery, we prepared a nanosized As2O3/Fe3O4 complex (Fe3O4 magnetic nanoparticles encapsulated in As2O3). Heating of certain organs or tissues to temperatures between 41°C-46°C (the procedure is termed tissue "hyperthermia") has been effective in tumor therapy. Nanoscaled magnetic fluid has been found to absorb much more energy than conventional materials, and this energy is further transferred to tumor cells resulting in tumor temperatures of 42°C-45°C. This process, termed "Magnetic Fluid Hyperthermia (MFH)" can be used for the treatment of either non-cancer diseases or tumors [1]. Numerous groups are working in this field worldwide, but only one approach has been tested in clinical trials so far
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