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dc.contributor.advisorTorres-Lugo, Madeline
dc.contributor.authorAlvarez-Berríos, Merlis P.
dc.description.abstractClinical 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.
dc.description.abstractEstudios clínicos han demostrado que hipertermia mejora la efectividad de drogas anti cáncer. Sin embargo, retos relacionados a la transferencia de calor ha limitado su aplicación a nivel clínico. El uso de fluidos magnéticos para inducir hipertermia (MFH) es una alternativa atractiva cuando es comparado con otras formas de hipertermia. Este tratamiento está basado en la liberación de calor de nanoparticulas magnéticas en presencia de un campo magnético. Estudios recientes han demostrado que hipertermia usando fluido magnético mejora el efecto terapéutico de agentes quimioterapéuticos. Sin embargo, los mecanismos celulares y moleculares por los cuales se produce este fenómeno requieren un conocimiento mas profundo, el cual es el enfoque de este trabajo. La hipótesis planteada es que al inducir hipertermia con nanopartículas magnéticas (MFH) inducirá efectos celulares importantes los cuales producirán una mayor citotoxicidad de drogas anti cáncer que han mostrado efectos clínicos limitados. Con el fin de probar esta hipótesis el efecto terapéutico de bortezomib (BZ) y cisplatin (cDDP) en combinación con MFH fue evaluado. Potenciales mecanismos para explicar nuestras previas observaciones sobre la potenciación terapéutica de estas drogas utilizando el calor disipado por nanopartículas magnéticas fueron elucidados. Finalmente, estudios preliminares in vivo fueron realizados con el fin de evaluar los efectos terapéuticos de cisplatino en combinación con MFH en modelos de animales. Nuestros resultados demuestran de forma concluyente que MFH produce marcados efectos celulares tales como fluidez membranal, daño de proteínas e inestabilidad de los microtúbulos, los cuales son responsables de la potenciación observada entre BZ o cDDP y MFH. Estudios in vivo mostraron que MFH aumentó la efectividad terapéutica de cisplatino. Este tratamiento podría convertirse en una plataforma potencialmente eficaz para el tratamiento de cáncer, incluso en aquellas líneas celulares que muestran resistencia intrínseca a dichas drogas.
dc.description.sponsorshipU.S. National Science Foundation, PR Institute for Functional Nanomaterials, US National Institutes of Healthen_US
dc.subjectAnticancer drugsen_US
dc.subjectMagnetic fluid hyperthermiaen_US
dc.subject.lcshMagnetic nanoparticle hyperthermiaen_US
dc.subject.lcshAntineoplastic agentsen_US
dc.subject.lcshDrug synergismen_US
dc.titleEnhanced potentiation of anticancer drugs using magnetic fluid hyperthermia (MFH): In vitro and in vivo studiesen_US
dc.rights.licenseAll rights reserveden_US
dc.rights.holder(c) 2014 Merlis P. Alvarez-Berriosen_US
dc.contributor.committeeRinaldi-Ramos, Carlos
dc.contributor.committeeOrtiz-Bermudez, Patricia
dc.contributor.committeeAcevedo-Rullán, Aldo
dc.contributor.representativeCastellanos, Dorial Engineeringen_US
dc.contributor.collegeCollege of Engineeringen_US
dc.contributor.departmentDepartment of Chemical Engineeringen_US

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