Efficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA)

Shaoyin Wei,1 Sijie Zhou,1 Wenjuan Huang,1,2 Xingjie Zan,1,3 Wujun Geng4 1School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, People’s Republic of China; 2Taizhou Hospital of Zhejiang Province Affiliat...

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Autores principales:	Wei S, Zhou S, Huang W, Zan X, Geng W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	antibody intracellular delivery coordination polymer nanocarrier peptide assembly Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/07e3c7be5edd46a2a44073f453035349
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spelling	oai:doaj.org-article:07e3c7be5edd46a2a44073f4530353492021-12-02T19:39:01ZEfficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA)1178-2013https://doaj.org/article/07e3c7be5edd46a2a44073f4530353492021-11-01T00:00:00Zhttps://www.dovepress.com/efficient-delivery-of-antibodies-intracellularly-by-co-assembly-with-h-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Shaoyin Wei,1 Sijie Zhou,1 Wenjuan Huang,1,2 Xingjie Zan,1,3 Wujun Geng4 1School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, People’s Republic of China; 2Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, 317000, Zhejiang Province, People’s Republic of China; 3Oujiang Laboratory, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, Zhejiang Province, People’s Republic of China; 4Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xingjie Zan; Wujun Geng Email xjzan2000@hotmail.com; gengwujun@126.comPurpose: There has been a substantial global market for antibodies, which are based on extracellular targets. Binding intracellular targets by antibodies will bring new chances in antibody therapeutics and a huge market increase. We aim to evaluate the efficiency of a novel delivery system of His6-metal assembly (HmA) in delivering intracellular antibodies and biofunctions of delivered antibodies.Methods: In this study, the physicochemical properties of HmA@Antibodies generated through co-assembling with antibodies and HmA were well characterized by dynamic light scatter. The cytotoxicity of HmA@Antibodies was investigated by Cell Counting Kit-8 (CCK-8). The endocytic kinetics and lysosome escape process of HmA@Antibodies were studied by flow cytometry and fluorescent staining imaging, respectively. Compared to the commercialized positive control, the intracellular delivery efficiency by HmA@Antibodies and biofunctions of delivered antibodies were evaluated by fluorescent imaging and CCK-8.Results: Various antibodies (IgG, anti-β-tubulin and anti-NPC) could co-assemble with HmA under a gentle condition, producing nano-sized (∼ 150 nm) and positively charged (∼+30 eV) HmA@Antibodies particles with narrow size distribution (PDI ∼ 0.15). HmA displayed very low cytotoxicity to divers cells (DCs, HeLa, HCECs, and HRPE) even after 96 h for the feeding concentration ≤ 100 μg mL− 1, and fast escape from endosomes. In the case of delivery IgG, the delivery efficiency into alive cells of HmA was better than a commercial protein delivery reagent (PULSin). For cases of the anti-β-tubulin and anti-NPC, HmA showed comparable delivery efficiency to their positive controls, but HmA with ability to deliver these antibodies into alive cells was still superior to positive controls delivering antibodies into dead cells through punching holes.Conclusion: Our results indicate that this strategy is a feasible way to deliver various antibodies intracellularly while preserving their functions, which has great potential in various applications and treating many refractory diseases by intracellular antibody delivery.Keywords: antibody, intracellular delivery, coordination polymer, nanocarrier, peptide assemblyWei SZhou SHuang WZan XGeng WDove Medical Pressarticleantibodyintracellular deliverycoordination polymernanocarrierpeptide assemblyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 7449-7461 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibody intracellular delivery coordination polymer nanocarrier peptide assembly Medicine (General) R5-920
spellingShingle	antibody intracellular delivery coordination polymer nanocarrier peptide assembly Medicine (General) R5-920 Wei S Zhou S Huang W Zan X Geng W Efficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA)
description	Shaoyin Wei,1 Sijie Zhou,1 Wenjuan Huang,1,2 Xingjie Zan,1,3 Wujun Geng4 1School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, People’s Republic of China; 2Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, 317000, Zhejiang Province, People’s Republic of China; 3Oujiang Laboratory, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, Zhejiang Province, People’s Republic of China; 4Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xingjie Zan; Wujun Geng Email xjzan2000@hotmail.com; gengwujun@126.comPurpose: There has been a substantial global market for antibodies, which are based on extracellular targets. Binding intracellular targets by antibodies will bring new chances in antibody therapeutics and a huge market increase. We aim to evaluate the efficiency of a novel delivery system of His6-metal assembly (HmA) in delivering intracellular antibodies and biofunctions of delivered antibodies.Methods: In this study, the physicochemical properties of HmA@Antibodies generated through co-assembling with antibodies and HmA were well characterized by dynamic light scatter. The cytotoxicity of HmA@Antibodies was investigated by Cell Counting Kit-8 (CCK-8). The endocytic kinetics and lysosome escape process of HmA@Antibodies were studied by flow cytometry and fluorescent staining imaging, respectively. Compared to the commercialized positive control, the intracellular delivery efficiency by HmA@Antibodies and biofunctions of delivered antibodies were evaluated by fluorescent imaging and CCK-8.Results: Various antibodies (IgG, anti-β-tubulin and anti-NPC) could co-assemble with HmA under a gentle condition, producing nano-sized (∼ 150 nm) and positively charged (∼+30 eV) HmA@Antibodies particles with narrow size distribution (PDI ∼ 0.15). HmA displayed very low cytotoxicity to divers cells (DCs, HeLa, HCECs, and HRPE) even after 96 h for the feeding concentration ≤ 100 μg mL− 1, and fast escape from endosomes. In the case of delivery IgG, the delivery efficiency into alive cells of HmA was better than a commercial protein delivery reagent (PULSin). For cases of the anti-β-tubulin and anti-NPC, HmA showed comparable delivery efficiency to their positive controls, but HmA with ability to deliver these antibodies into alive cells was still superior to positive controls delivering antibodies into dead cells through punching holes.Conclusion: Our results indicate that this strategy is a feasible way to deliver various antibodies intracellularly while preserving their functions, which has great potential in various applications and treating many refractory diseases by intracellular antibody delivery.Keywords: antibody, intracellular delivery, coordination polymer, nanocarrier, peptide assembly
format	article
author	Wei S Zhou S Huang W Zan X Geng W
author_facet	Wei S Zhou S Huang W Zan X Geng W
author_sort	Wei S
title	Efficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA)
title_short	Efficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA)
title_full	Efficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA)
title_fullStr	Efficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA)
title_full_unstemmed	Efficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA)
title_sort	efficient delivery of antibodies intracellularly by co-assembly with hexahistidine-metal assemblies (hma)
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/07e3c7be5edd46a2a44073f453035349
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Efficient Delivery of Antibodies Intracellularly by Co-Assembly with Hexahistidine-Metal Assemblies (HmA)

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