Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery

Lingxiao Xie, Xiong Ding, Rachel Budry, Guangzhao Mao Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI, USA Background: The layer-by-layer (LbL) assembly method offers a molecular level control of the amount and spatial distribution of bioactive molecul...

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Autores principales:	Xie L, Ding X, Budry R, Mao G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Biodegradable polymers cell transfection interlayer diffusion localized gene delivery polyelectrolyte multilayers sequential release Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e52299c1dff54520be989c3a01a2c15e
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spelling	oai:doaj.org-article:e52299c1dff54520be989c3a01a2c15e2021-12-02T07:22:20ZLayer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery1178-2013https://doaj.org/article/e52299c1dff54520be989c3a01a2c15e2018-08-01T00:00:00Zhttps://www.dovepress.com/layer-by-layer-dna-films-incorporating-highly-transfecting-bioreducibl-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lingxiao Xie, Xiong Ding, Rachel Budry, Guangzhao Mao Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI, USA Background: The layer-by-layer (LbL) assembly method offers a molecular level control of the amount and spatial distribution of bioactive molecules. However, successful clinical translation of LbL film technology will most certainly require a better understanding and control of not only the film assembly process, but also film disassembly kinetics in physiologic conditions. Purpose: This work focuses on the understanding and control of degradation properties of LbL films for localized gene delivery. Methods: Bioreducible poly(amido amine)s (PAAs) containing cystaminebisacrylamide (CBA), methylenebisacrylamide, and 5-amino-1-pentanol (APOL) were synthesized by Michael addition polymerization for the construction of bioreducible LbL films capable of sequential gene delivery. Results: The synthesized PAAs were screened for desirable buffering capacity, cell transfection, and cytotoxicity characteristics together with 25 kDa branched polyethylenimine (PEI) and cross-linked 800 Da PEI. By screening the various polycations we were able to identify a copolymer of CBA and APOL for the subsequent construction of the LbL films. By incorporating a highly transfecting polycation and a nondiffusing polycation we were able to improve the overall transfection of HEK293 and MC3T3 cells from the bioreducible LbL films. We also demonstrated the dual-stage release and transfection of two different DNAs from the LbL films. Conclusion: The results indicate that LbL films consisting of bioreducible PAAs and non-diffusing polyelectrolytes have excellent degradation properties for the development of LbL coating technology for localized gene delivery applications. Keywords: biodegradable polymers, cell transfection, interlayer diffusion, localized gene delivery, polyelectrolyte multilayers, sequential releaseXie LDing XBudry RMao GDove Medical PressarticleBiodegradable polymerscell transfectioninterlayer diffusionlocalized gene deliverypolyelectrolyte multilayerssequential releaseMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4943-4960 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biodegradable polymers cell transfection interlayer diffusion localized gene delivery polyelectrolyte multilayers sequential release Medicine (General) R5-920
spellingShingle	Biodegradable polymers cell transfection interlayer diffusion localized gene delivery polyelectrolyte multilayers sequential release Medicine (General) R5-920 Xie L Ding X Budry R Mao G Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery
description	Lingxiao Xie, Xiong Ding, Rachel Budry, Guangzhao Mao Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI, USA Background: The layer-by-layer (LbL) assembly method offers a molecular level control of the amount and spatial distribution of bioactive molecules. However, successful clinical translation of LbL film technology will most certainly require a better understanding and control of not only the film assembly process, but also film disassembly kinetics in physiologic conditions. Purpose: This work focuses on the understanding and control of degradation properties of LbL films for localized gene delivery. Methods: Bioreducible poly(amido amine)s (PAAs) containing cystaminebisacrylamide (CBA), methylenebisacrylamide, and 5-amino-1-pentanol (APOL) were synthesized by Michael addition polymerization for the construction of bioreducible LbL films capable of sequential gene delivery. Results: The synthesized PAAs were screened for desirable buffering capacity, cell transfection, and cytotoxicity characteristics together with 25 kDa branched polyethylenimine (PEI) and cross-linked 800 Da PEI. By screening the various polycations we were able to identify a copolymer of CBA and APOL for the subsequent construction of the LbL films. By incorporating a highly transfecting polycation and a nondiffusing polycation we were able to improve the overall transfection of HEK293 and MC3T3 cells from the bioreducible LbL films. We also demonstrated the dual-stage release and transfection of two different DNAs from the LbL films. Conclusion: The results indicate that LbL films consisting of bioreducible PAAs and non-diffusing polyelectrolytes have excellent degradation properties for the development of LbL coating technology for localized gene delivery applications. Keywords: biodegradable polymers, cell transfection, interlayer diffusion, localized gene delivery, polyelectrolyte multilayers, sequential release
format	article
author	Xie L Ding X Budry R Mao G
author_facet	Xie L Ding X Budry R Mao G
author_sort	Xie L
title	Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery
title_short	Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery
title_full	Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery
title_fullStr	Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery
title_full_unstemmed	Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery
title_sort	layer-by-layer dna films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/e52299c1dff54520be989c3a01a2c15e
work_keys_str_mv	AT xiel layerbylayerdnafilmsincorporatinghighlytransfectingbioreduciblepolyamidoamineandpolyethylenimineforsequentialgenedelivery AT dingx layerbylayerdnafilmsincorporatinghighlytransfectingbioreduciblepolyamidoamineandpolyethylenimineforsequentialgenedelivery AT budryr layerbylayerdnafilmsincorporatinghighlytransfectingbioreduciblepolyamidoamineandpolyethylenimineforsequentialgenedelivery AT maog layerbylayerdnafilmsincorporatinghighlytransfectingbioreduciblepolyamidoamineandpolyethylenimineforsequentialgenedelivery
_version_	1718399489253834752

Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery

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