In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer

Fernando Mérida, 1 Carlos Rinaldi, 2, 3 Eduardo J Juan, 4 Madeline Torres-Lugo 1 1Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto Rico; 2Department of Chemical Engineering, University of Florida, Gainesville, FL, USA; 3J. Crayt...

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Autores principales:	Mérida F, Rinaldi C, Juan EJ, Torres-Lugo M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	mfh ultrasound sonoporation microbubble pes membrane permeabilization enhanced cytotoxicity. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/447a41d2b2234a5c911374fbf3a3ffa4
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spelling	oai:doaj.org-article:447a41d2b2234a5c911374fbf3a3ffa42021-12-02T08:18:59ZIn vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer1178-2013https://doaj.org/article/447a41d2b2234a5c911374fbf3a3ffa42020-01-01T00:00:00Zhttps://www.dovepress.com/in-vitro-ultrasonic-potentiation-of-2-phenylethynesulfonamidemagnetic--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fernando Mérida, 1 Carlos Rinaldi, 2, 3 Eduardo J Juan, 4 Madeline Torres-Lugo 1 1Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto Rico; 2Department of Chemical Engineering, University of Florida, Gainesville, FL, USA; 3J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; 4Department of Electrical and Computer Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto RicoCorrespondence: Madeline Torres-Lugo Road 108 Km. 1.0 Bo. Miradero. P.O. Box 9046, Mayagüez 00681-9046, Puerto RicoTel +1787 832 4040 Ext. 2585Email madeline@ece.uprm.eduBackground: Magnetic Fluid Hyperthermia (MFH) is a promising adjuvant for chemotherapy, potentiating the action of anticancer agents. However, drug delivery to cancer cells must be optimized to improve the overall therapeutic effect of drug/MFH combination treatments.Purpose: The aim of this work was to demonstrate the potentiation of 2-phenylethynesulfonamide (PES) at various combination treatments with MFH, using low-intensity ultrasound as an intracellular delivery enhancer.Methods: The effect of ultrasound (US), MFH, and PES was first evaluated individually and then as combination treatments. Definity® microbubbles and polyethylene glycol (PEG)-coated iron oxide nanoparticles were used to induce cell sonoporation and MFH, respectively. Assessment of cell membrane permeabilization was evaluated via fluorescence microscopy, iron uptake by cells was quantified by UV-Vis spectroscopy, and cell viability was determined using automatic cell counting.Results: Notable reductions in cancer cell viability were observed when ultrasound was incorporated. For example, the treatment US+PES reduced cell viability by 37% compared to the non-toxic effect of the drug. Similarly, the treatment US+MFH using mild hyperthermia (41°C), reduced cell viability by an additional 18% when compared to the effect of MH alone. Significant improvements were observed for the combination of US+PES+MFH with cell viability reduced by an additional 26% compared to the PES+MFH group. The improved cytotoxicity was attributed to enhanced drug/nanoparticle intracellular delivery, with iron uptake values nearly twice those achieved without ultrasound. Various treatment schedules were examined, and all of them showed substantial cell death, indicating that the time elapsed between sonoporation and magnetic field exposure was not significant.Conclusion: Superior cancer cell-killing patterns took place when ultrasound was incorporated thus demonstrating the in vitro ultrasonic potentiation of PES and mild MFH. This work demonstrated that ultrasound is a promising non-invasive enhancer of PES/MFH combination treatments, aiming to establish a sono-thermo-chemotherapy in the treatment of ovarian cancer.Keywords: MFH, ultrasound, sonoporation, microbubble, PES, membrane permeabilization, enhanced cytotoxicityMérida FRinaldi CJuan EJTorres-Lugo MDove Medical Pressarticlemfhultrasoundsonoporationmicrobubblepesmembrane permeabilizationenhanced cytotoxicity.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 419-432 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	mfh ultrasound sonoporation microbubble pes membrane permeabilization enhanced cytotoxicity. Medicine (General) R5-920
spellingShingle	mfh ultrasound sonoporation microbubble pes membrane permeabilization enhanced cytotoxicity. Medicine (General) R5-920 Mérida F Rinaldi C Juan EJ Torres-Lugo M In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer
description	Fernando Mérida, 1 Carlos Rinaldi, 2, 3 Eduardo J Juan, 4 Madeline Torres-Lugo 1 1Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto Rico; 2Department of Chemical Engineering, University of Florida, Gainesville, FL, USA; 3J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; 4Department of Electrical and Computer Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto RicoCorrespondence: Madeline Torres-Lugo Road 108 Km. 1.0 Bo. Miradero. P.O. Box 9046, Mayagüez 00681-9046, Puerto RicoTel +1787 832 4040 Ext. 2585Email madeline@ece.uprm.eduBackground: Magnetic Fluid Hyperthermia (MFH) is a promising adjuvant for chemotherapy, potentiating the action of anticancer agents. However, drug delivery to cancer cells must be optimized to improve the overall therapeutic effect of drug/MFH combination treatments.Purpose: The aim of this work was to demonstrate the potentiation of 2-phenylethynesulfonamide (PES) at various combination treatments with MFH, using low-intensity ultrasound as an intracellular delivery enhancer.Methods: The effect of ultrasound (US), MFH, and PES was first evaluated individually and then as combination treatments. Definity® microbubbles and polyethylene glycol (PEG)-coated iron oxide nanoparticles were used to induce cell sonoporation and MFH, respectively. Assessment of cell membrane permeabilization was evaluated via fluorescence microscopy, iron uptake by cells was quantified by UV-Vis spectroscopy, and cell viability was determined using automatic cell counting.Results: Notable reductions in cancer cell viability were observed when ultrasound was incorporated. For example, the treatment US+PES reduced cell viability by 37% compared to the non-toxic effect of the drug. Similarly, the treatment US+MFH using mild hyperthermia (41°C), reduced cell viability by an additional 18% when compared to the effect of MH alone. Significant improvements were observed for the combination of US+PES+MFH with cell viability reduced by an additional 26% compared to the PES+MFH group. The improved cytotoxicity was attributed to enhanced drug/nanoparticle intracellular delivery, with iron uptake values nearly twice those achieved without ultrasound. Various treatment schedules were examined, and all of them showed substantial cell death, indicating that the time elapsed between sonoporation and magnetic field exposure was not significant.Conclusion: Superior cancer cell-killing patterns took place when ultrasound was incorporated thus demonstrating the in vitro ultrasonic potentiation of PES and mild MFH. This work demonstrated that ultrasound is a promising non-invasive enhancer of PES/MFH combination treatments, aiming to establish a sono-thermo-chemotherapy in the treatment of ovarian cancer.Keywords: MFH, ultrasound, sonoporation, microbubble, PES, membrane permeabilization, enhanced cytotoxicity
format	article
author	Mérida F Rinaldi C Juan EJ Torres-Lugo M
author_facet	Mérida F Rinaldi C Juan EJ Torres-Lugo M
author_sort	Mérida F
title	In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer
title_short	In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer
title_full	In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer
title_fullStr	In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer
title_full_unstemmed	In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer
title_sort	in vitro ultrasonic potentiation of 2-phenylethynesulfonamide/magnetic fluid hyperthermia combination treatments for ovarian cancer
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/447a41d2b2234a5c911374fbf3a3ffa4
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In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer

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