Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing

Abstract Irreversible electroporation (IRE) is used clinically as a focal therapy to ablate solid tumors. A critical disadvantage of IRE as a monotherapy for cancer is the inability of ablating large tumors, because the electric field strength required is often too high to be safe. Previous reports...

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Autores principales:	Samuel M. Hanson, Bruce Forsyth, Chun Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/63d1690252c347079afdff9d613e9892
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spelling	oai:doaj.org-article:63d1690252c347079afdff9d613e98922021-12-02T15:00:40ZCombination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing10.1038/s41598-021-89661-y2045-2322https://doaj.org/article/63d1690252c347079afdff9d613e98922021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89661-yhttps://doaj.org/toc/2045-2322Abstract Irreversible electroporation (IRE) is used clinically as a focal therapy to ablate solid tumors. A critical disadvantage of IRE as a monotherapy for cancer is the inability of ablating large tumors, because the electric field strength required is often too high to be safe. Previous reports indicate that cells exposed to certain cationic small molecules and surfactants are more vulnerable to IRE at lower electric field strengths. However, low-molecular-weight IRE sensitizers may suffer from suboptimal bioavailability due to poor stability and a lack of control over spatiotemporal accumulation in the tumor tissue. Here, we show that a synthetic membranolytic polymer, poly(6-aminohexyl methacrylate) (PAHM), synergizes with IRE to achieve enhanced cancer cell killing. The enhanced efficacy of the combination therapy is attributed to PAHM-mediated sensitization of cancer cells to IRE and to the direct cell killing by PAHM through membrane lysis. We further demonstrate sustained release of PAHM from embolic beads over 1 week in physiological medium. Taken together, combining IRE and a synthetic macromolecular sensitizer with intrinsic membranolytic activity and sustained bioavailability may present new therapeutic opportunities for a wide range of solid tumors.Samuel M. HansonBruce ForsythChun WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Samuel M. Hanson Bruce Forsyth Chun Wang Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing
description	Abstract Irreversible electroporation (IRE) is used clinically as a focal therapy to ablate solid tumors. A critical disadvantage of IRE as a monotherapy for cancer is the inability of ablating large tumors, because the electric field strength required is often too high to be safe. Previous reports indicate that cells exposed to certain cationic small molecules and surfactants are more vulnerable to IRE at lower electric field strengths. However, low-molecular-weight IRE sensitizers may suffer from suboptimal bioavailability due to poor stability and a lack of control over spatiotemporal accumulation in the tumor tissue. Here, we show that a synthetic membranolytic polymer, poly(6-aminohexyl methacrylate) (PAHM), synergizes with IRE to achieve enhanced cancer cell killing. The enhanced efficacy of the combination therapy is attributed to PAHM-mediated sensitization of cancer cells to IRE and to the direct cell killing by PAHM through membrane lysis. We further demonstrate sustained release of PAHM from embolic beads over 1 week in physiological medium. Taken together, combining IRE and a synthetic macromolecular sensitizer with intrinsic membranolytic activity and sustained bioavailability may present new therapeutic opportunities for a wide range of solid tumors.
format	article
author	Samuel M. Hanson Bruce Forsyth Chun Wang
author_facet	Samuel M. Hanson Bruce Forsyth Chun Wang
author_sort	Samuel M. Hanson
title	Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing
title_short	Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing
title_full	Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing
title_fullStr	Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing
title_full_unstemmed	Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing
title_sort	combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/63d1690252c347079afdff9d613e9892
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Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing

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