Thermochemotherapy effect of nanosized As2O3/Fe3O4 complex on experimental mouse tumors and its influence on the expression of CD44v6, VEGF-C and MMP-9

BACKGROUND 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 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. RESULTS The 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 degrees C to 65 degrees 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). CONCLUSION As2O3/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.