Alvarez-Berríos, Merlis P.
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Publication Enhanced potentiation of anticancer drugs using magnetic fluid hyperthermia (MFH): In vitro and in vivo studies(2014) Alvarez-Berríos, Merlis P.; Torres-Lugo, Madeline; College of Engineering; Rinaldi-Ramos, Carlos; Ortiz-Bermudez, Patricia; Acevedo-Rullán, Aldo; Department of Chemical Engineering; Castellanos, DorialClinical studies have demonstrated the effectiveness of combined hyperthermia and anticancer drug treatments. Challenges related to effective heat transfer have limited its clinical application. The use of magnetic fluids to induce hyperthermia is an attractive alternative to other forms of hyperthermia. It is based on the heat released by magnetic nanoparticles subjected to magnetic field. Recent studies have shown that magnetic fluid hyperthermia (MFH) enhances the therapeutic effects of chemotherapeutic agents. Knowledge regarding the underlying cellular and molecular mechanisms by which such phenomena occur requires more in depth understanding, and it is the focus of this work. It is hypothesized that by inducing hyperthermia via magnetic nanoparticles (MFH) significant cellular effects will be induced that will result in enhanced cytotoxicity of anticancer drugs, which currently possess limited clinical applications. For this purpose, in vitro therapeutic enhancement of bortezomib (BZ) and cisplatin (cDDP) using heat dissipated by magnetic nanoparticles was evaluated. Potential mechanisms to explain our observations of potentiation of these anti-cancer drugs by MFH were also elucidated. Finally, the in vivo therapeutic effects of cisplatin combined with MFH were assessed. Our results conclusively demonstrate that MFH produced marked cellular effects such as membrane fluidity, protein damage and microtubule instability, which were responsible for the in vitro enhanced potentiation between MFH and BZ or cDDP. In vivo studies showed therapeutic enhancement of cisplatin when combined with MFH. These results are significant because this approach could become a potentially effective anticancer therapy platform even in those cell lines that show intrinsic resistance to the drug.