Self-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification

Qianru Yu,1,* Maxin Zhang,1,* Yuetan Chen,1,* Xiaolong Chen,2 Sanyuan Shi,1 Kang Sun,1 Ran Ye,1 Yuan Zheng,1 Yang Chen,1 Yuhong Xu,1,3 Jinliang Peng1 1School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China; 2NanoDrug Platform, Zhejiang California Int...

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Autores principales:	Yu Q, Zhang M, Chen Y, Chen X, Shi S, Sun K, Ye R, Zheng Y, Xu Y, Peng J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	self-assembled nanoparticle pamam dendrimer polyethylenimine epidermal growth factor receptor variant iii chimeric antigen receptor t lymphocyte Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/507bb0afce354231b59790f657c6d27f
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spelling	oai:doaj.org-article:507bb0afce354231b59790f657c6d27f2021-12-02T04:35:12ZSelf-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification1178-2013https://doaj.org/article/507bb0afce354231b59790f657c6d27f2020-01-01T00:00:00Zhttps://www.dovepress.com/self-assembled-nanoparticles-prepared-from-low-molecular-weight-pei-an-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Qianru Yu,1,* Maxin Zhang,1,* Yuetan Chen,1,* Xiaolong Chen,2 Sanyuan Shi,1 Kang Sun,1 Ran Ye,1 Yuan Zheng,1 Yang Chen,1 Yuhong Xu,1,3 Jinliang Peng1 1School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China; 2NanoDrug Platform, Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou 310058, People’s Republic of China; 3School of Pharmacy and Chemistry, Dali University, Dali City 671000, People’s Republic of China *These authors contributed equally to this workCorrespondence: Jinliang PengSchool of Pharmacy, Shanghai Jiao Tong University, No. 800, Dongchuan Road, Shanghai 200240, People’s Republic of ChinaTel/Fax +86 21 3420 4739Email pjl76@sjtu.edu.cnBackground: The complex preparation procedures and severe toxicities are two major obstacles facing the wide use of chimeric antigen receptor-modified T (CAR-T) cells in clinical cancer immunotherapy. The nanotechnology-based T cell temporary CAR modification may be a potential approach to solve these problems and make the CAR-T cell-based tumor therapy feasible and broadly applicable.Methods: A series of plasmid DNA-loaded self-assembled nanoparticles (pDNA@SNPsx/y) prepared from adamantane-grafted polyamidoamine (Ad-PAMAM) dendrimers of different generations (G1 or G5) and cyclodextrin-grafted branched polyethylenimine (CD-PEI) of different molecular weights (800, 2000, or 25,000 Da) were characterized and evaluated. The detailed physicochemical properties, cellular interaction, and cytotoxicity of selected pDNA@SNPG1/800 were systematically investigated. Thereafter, the epidermal growth factor receptor variant III (EGFRvIII) CAR-expression plasmid vector (pEGFRvIII-CAR) was constructed and encapsulated into SNPG1/800. The resulting pEGFRvIII-CAR@SNPG1/800 was used for Jurkat cell transient transfection, and the EGFRvIII-CAR expressed in transfected cells was measured by flow cytometry and Western blot. Finally, the response of EGFRvIII CAR-positive Jurkat T cell to target tumor cell was evaluated.Results: The pDNA@SNPG1/800 showed the highest efficacy in Jurkat cell gene transfection and exhibited low cytotoxicity. pEGFRvIII-CAR@SNPG1/800 can efficiently deliver pEGFRvIII-CAR into Jurkat T cells, thereby resulting in transient EGFRvIII-CAR expression in transfected cells. EGFRvIII-CAR that is present on the cell membrane enabled Jurkat T cells to recognize and bind specifically with EGFRvIII-positive tumor cells.Conclusion: These results indicated that pEGFRvIII-CAR@SNPG1/800 can effectively achieve T-cell transient CAR modification, thereby demonstrating considerable potential in CAR-T cancer therapy.Keywords: self-assembled nanoparticle, PAMAM dendrimer, polyethylenimine, epidermal growth factor receptor variant III, chimeric antigen receptor, T lymphocyteYu QZhang MChen YChen XShi SSun KYe RZheng YChen YXu YPeng JDove Medical Pressarticleself-assembled nanoparticlepamam dendrimerpolyethylenimineepidermal growth factor receptor variant iiichimeric antigen receptort lymphocyteMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 483-495 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	self-assembled nanoparticle pamam dendrimer polyethylenimine epidermal growth factor receptor variant iii chimeric antigen receptor t lymphocyte Medicine (General) R5-920
spellingShingle	self-assembled nanoparticle pamam dendrimer polyethylenimine epidermal growth factor receptor variant iii chimeric antigen receptor t lymphocyte Medicine (General) R5-920 Yu Q Zhang M Chen Y Chen X Shi S Sun K Ye R Zheng Y Chen Y Xu Y Peng J Self-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification
description	Qianru Yu,1,* Maxin Zhang,1,* Yuetan Chen,1,* Xiaolong Chen,2 Sanyuan Shi,1 Kang Sun,1 Ran Ye,1 Yuan Zheng,1 Yang Chen,1 Yuhong Xu,1,3 Jinliang Peng1 1School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China; 2NanoDrug Platform, Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou 310058, People’s Republic of China; 3School of Pharmacy and Chemistry, Dali University, Dali City 671000, People’s Republic of China *These authors contributed equally to this workCorrespondence: Jinliang PengSchool of Pharmacy, Shanghai Jiao Tong University, No. 800, Dongchuan Road, Shanghai 200240, People’s Republic of ChinaTel/Fax +86 21 3420 4739Email pjl76@sjtu.edu.cnBackground: The complex preparation procedures and severe toxicities are two major obstacles facing the wide use of chimeric antigen receptor-modified T (CAR-T) cells in clinical cancer immunotherapy. The nanotechnology-based T cell temporary CAR modification may be a potential approach to solve these problems and make the CAR-T cell-based tumor therapy feasible and broadly applicable.Methods: A series of plasmid DNA-loaded self-assembled nanoparticles (pDNA@SNPsx/y) prepared from adamantane-grafted polyamidoamine (Ad-PAMAM) dendrimers of different generations (G1 or G5) and cyclodextrin-grafted branched polyethylenimine (CD-PEI) of different molecular weights (800, 2000, or 25,000 Da) were characterized and evaluated. The detailed physicochemical properties, cellular interaction, and cytotoxicity of selected pDNA@SNPG1/800 were systematically investigated. Thereafter, the epidermal growth factor receptor variant III (EGFRvIII) CAR-expression plasmid vector (pEGFRvIII-CAR) was constructed and encapsulated into SNPG1/800. The resulting pEGFRvIII-CAR@SNPG1/800 was used for Jurkat cell transient transfection, and the EGFRvIII-CAR expressed in transfected cells was measured by flow cytometry and Western blot. Finally, the response of EGFRvIII CAR-positive Jurkat T cell to target tumor cell was evaluated.Results: The pDNA@SNPG1/800 showed the highest efficacy in Jurkat cell gene transfection and exhibited low cytotoxicity. pEGFRvIII-CAR@SNPG1/800 can efficiently deliver pEGFRvIII-CAR into Jurkat T cells, thereby resulting in transient EGFRvIII-CAR expression in transfected cells. EGFRvIII-CAR that is present on the cell membrane enabled Jurkat T cells to recognize and bind specifically with EGFRvIII-positive tumor cells.Conclusion: These results indicated that pEGFRvIII-CAR@SNPG1/800 can effectively achieve T-cell transient CAR modification, thereby demonstrating considerable potential in CAR-T cancer therapy.Keywords: self-assembled nanoparticle, PAMAM dendrimer, polyethylenimine, epidermal growth factor receptor variant III, chimeric antigen receptor, T lymphocyte
format	article
author	Yu Q Zhang M Chen Y Chen X Shi S Sun K Ye R Zheng Y Chen Y Xu Y Peng J
author_facet	Yu Q Zhang M Chen Y Chen X Shi S Sun K Ye R Zheng Y Chen Y Xu Y Peng J
author_sort	Yu Q
title	Self-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification
title_short	Self-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification
title_full	Self-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification
title_fullStr	Self-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification
title_full_unstemmed	Self-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification
title_sort	self-assembled nanoparticles prepared from low-molecular-weight pei and low-generation pamam for egfrviii-chimeric antigen receptor gene loading and t-cell transient modification
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/507bb0afce354231b59790f657c6d27f
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Self-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification

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