Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery

Gene therapy is a promising treatment for hereditary diseases, as well as acquired genetic diseases, including cancer. Facing the complicated physiological and pathological environment in vivo, developing efficient non-viral gene vectors is needed for their clinical application. Here, poly(<i>...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Huaiying Zhang, Damla Keskin, Willy H. de Haan-Visser, Guangyue Zu, Patrick van Rijn, Inge S. Zuhorn
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	nanogels gene delivery endosomal escape quaternization aliphatic chains Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/d7ab6458ceae48b59d21b301d3a768ab
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d7ab6458ceae48b59d21b301d3a768ab
record_format	dspace
spelling	oai:doaj.org-article:d7ab6458ceae48b59d21b301d3a768ab2021-11-25T18:42:26ZAliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery10.3390/pharmaceutics131119641999-4923https://doaj.org/article/d7ab6458ceae48b59d21b301d3a768ab2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1964https://doaj.org/toc/1999-4923Gene therapy is a promising treatment for hereditary diseases, as well as acquired genetic diseases, including cancer. Facing the complicated physiological and pathological environment in vivo, developing efficient non-viral gene vectors is needed for their clinical application. Here, poly(<i>N</i>-isopropylacrylamide) (p(NIPAM)) nanogels are presented with either protonatable tertiary amine groups or permanently charged quaternized ammonium groups to achieve DNA complexation ability. In addition, a quaternary ammonium-functionalized nanogel was further provided with an aliphatic moiety using 1-bromododecane to add a membrane-interacting structure to ultimately facilitate intracellular release of the genetic material. The ability of the tertiary amine-, quaternized ammonium-, and aliphatic quaternized ammonium-functionalized p(NIPAM) nanogels (i.e., NGs, NGs-MI, and NGs-BDD, respectively) to mediate gene transfection was evaluated by fluorescence microscopy and flow cytometry. It is observed that NGs-BDD/pDNA complexes exhibit efficient gene loading, gene protection ability, and intracellular uptake similar to that of NGs-MI/pDNA complexes. However, only the NGs-BDD/pDNA complexes show a notable gene transfer efficiency, which can be ascribed to their ability to mediate DNA escape from endosomes. We conclude that NGs-BDD displays a cationic lipid-like behavior that facilitates endosomal escape by perturbing the endosomal/lysosomal membrane. These findings demonstrate that the presence of aliphatic chains within the nanogel is instrumental in accomplishing gene delivery, which provides a rationale for the further development of nanogel-based gene delivery systems.Huaiying ZhangDamla KeskinWilly H. de Haan-VisserGuangyue ZuPatrick van RijnInge S. ZuhornMDPI AGarticlenanogelsgene deliveryendosomal escapequaternizationaliphatic chainsPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1964, p 1964 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanogels gene delivery endosomal escape quaternization aliphatic chains Pharmacy and materia medica RS1-441
spellingShingle	nanogels gene delivery endosomal escape quaternization aliphatic chains Pharmacy and materia medica RS1-441 Huaiying Zhang Damla Keskin Willy H. de Haan-Visser Guangyue Zu Patrick van Rijn Inge S. Zuhorn Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery
description	Gene therapy is a promising treatment for hereditary diseases, as well as acquired genetic diseases, including cancer. Facing the complicated physiological and pathological environment in vivo, developing efficient non-viral gene vectors is needed for their clinical application. Here, poly(<i>N</i>-isopropylacrylamide) (p(NIPAM)) nanogels are presented with either protonatable tertiary amine groups or permanently charged quaternized ammonium groups to achieve DNA complexation ability. In addition, a quaternary ammonium-functionalized nanogel was further provided with an aliphatic moiety using 1-bromododecane to add a membrane-interacting structure to ultimately facilitate intracellular release of the genetic material. The ability of the tertiary amine-, quaternized ammonium-, and aliphatic quaternized ammonium-functionalized p(NIPAM) nanogels (i.e., NGs, NGs-MI, and NGs-BDD, respectively) to mediate gene transfection was evaluated by fluorescence microscopy and flow cytometry. It is observed that NGs-BDD/pDNA complexes exhibit efficient gene loading, gene protection ability, and intracellular uptake similar to that of NGs-MI/pDNA complexes. However, only the NGs-BDD/pDNA complexes show a notable gene transfer efficiency, which can be ascribed to their ability to mediate DNA escape from endosomes. We conclude that NGs-BDD displays a cationic lipid-like behavior that facilitates endosomal escape by perturbing the endosomal/lysosomal membrane. These findings demonstrate that the presence of aliphatic chains within the nanogel is instrumental in accomplishing gene delivery, which provides a rationale for the further development of nanogel-based gene delivery systems.
format	article
author	Huaiying Zhang Damla Keskin Willy H. de Haan-Visser Guangyue Zu Patrick van Rijn Inge S. Zuhorn
author_facet	Huaiying Zhang Damla Keskin Willy H. de Haan-Visser Guangyue Zu Patrick van Rijn Inge S. Zuhorn
author_sort	Huaiying Zhang
title	Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery
title_short	Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery
title_full	Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery
title_fullStr	Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery
title_full_unstemmed	Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery
title_sort	aliphatic quaternary ammonium functionalized nanogels for gene delivery
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d7ab6458ceae48b59d21b301d3a768ab
work_keys_str_mv	AT huaiyingzhang aliphaticquaternaryammoniumfunctionalizednanogelsforgenedelivery AT damlakeskin aliphaticquaternaryammoniumfunctionalizednanogelsforgenedelivery AT willyhdehaanvisser aliphaticquaternaryammoniumfunctionalizednanogelsforgenedelivery AT guangyuezu aliphaticquaternaryammoniumfunctionalizednanogelsforgenedelivery AT patrickvanrijn aliphaticquaternaryammoniumfunctionalizednanogelsforgenedelivery AT ingeszuhorn aliphaticquaternaryammoniumfunctionalizednanogelsforgenedelivery
_version_	1718410802237538304

Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery

Ejemplares similares