Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells

Heng Dong,1,2,* Zhi-Fa Wen,2,3,* Lin Chen,1 Na Zhou,1 Hui Liu,1 Shiling Dong,1 Hong-ming Hu,2 Yongbin Mou11Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 2Laboratory of Cancer Immunobiology, Robert W Franz Cancer Research Center, Earle A Ch...

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Autores principales:	Dong H, Wen ZF, Chen L, Zhou N, Liu H, Dong S, Hu HM, Mou YB
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	aluminum hydroxide antigen delivery DRibbles nano-adjuvant cancer immunotherapy autophagosome. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e7e10d8c0b9a405a9f387b73e3cd389b
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spelling	oai:doaj.org-article:e7e10d8c0b9a405a9f387b73e3cd389b2021-12-02T04:04:09ZPolyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells1178-2013https://doaj.org/article/e7e10d8c0b9a405a9f387b73e3cd389b2018-06-01T00:00:00Zhttps://www.dovepress.com/polyethyleneimine-modification-of-aluminum-hydroxide-nanoparticle-enha-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Heng Dong,1,2,* Zhi-Fa Wen,2,3,* Lin Chen,1 Na Zhou,1 Hui Liu,1 Shiling Dong,1 Hong-ming Hu,2 Yongbin Mou11Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 2Laboratory of Cancer Immunobiology, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center, Portland, OR, USA; 3Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, China*These authors contributed equally to this workBackground: The aim of this study was to explore the feasibility of delivering tumor antigens and enhancing the antigen cross-presentation of dendritic cells (DCs) by aluminum hydroxide nanoparticle with polyethyleneimine (PEI) modification (LV@HPA/PEI). Materials and methods: The LV@HPA nanoparticles were modified by PEI first, then the influence of LV@HPA/PEI on DCs was examined. The distinct expression of ovalbumin (OVA) protein transported into DCs by LV@HPA/PEI was observed by flow cytometry and Western blot. The biocompatibility of LV@HPA/PEI, maturity and antigen cross-presentation of DCs was observed in vitro. Tumor derived autophagosomes (DRibbles) combined with LV@HPA/PEI were loaded into DCs, and DC vaccines were used to immunize mice. The percentage of CD3+CD8+IFN-γ+ T cells in immunized mice was determined by flow cytometry. Additionally, the functional properties of the LV@HPA/PEI-DRibble-DCs vaccine were examined in vivo in PancO2 tumor-bearing mice.Results: In our study, we described how LV@HPA/PEI can be a functionalized antigen delivery system with notable antigen transport effect and negligible cytotoxicity. It was found that LV@HPA/PEI could be easily internalized into DCs to assist antigen release into the cytoplasm. In addition, DCs matured gradually after loading with LV@HPA/PEI-OVA, which increased significantly the cytokine IL-12 secretion and expression of surface molecules CD80 and CD86. Interestingly, DCs loaded with LV@HPA/PEI-DRibbles could promote the activation of tumor-specific T cells both in murine and in human T cells. In the following in vivo experiments, the vaccine of LV@HPA/PEI-DRibble-DCs significantly inhibited tumor growth and improved the survival rate of the PancO2 tumor-bearing mice.Conclusion: We established a high-performance anti-tumor vaccine of DCs loaded with LV@HPA/PEI nanoparticles and tumor-associated antigens in autophagosomes (DRibbles), which could serve as a therapeutic strategy in cancer immunotherapy.Keywords: aluminum hydroxide, antigen delivery, DRibbles, nano-adjuvant, cancer immunotherapy, autophagosomeDong HWen ZFChen LZhou NLiu HDong SHu HMMou YBDove Medical Pressarticlealuminum hydroxideantigen deliveryDRibblesnano-adjuvantcancer immunotherapyautophagosome.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3353-3365 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	aluminum hydroxide antigen delivery DRibbles nano-adjuvant cancer immunotherapy autophagosome. Medicine (General) R5-920
spellingShingle	aluminum hydroxide antigen delivery DRibbles nano-adjuvant cancer immunotherapy autophagosome. Medicine (General) R5-920 Dong H Wen ZF Chen L Zhou N Liu H Dong S Hu HM Mou YB Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells
description	Heng Dong,1,2,* Zhi-Fa Wen,2,3,* Lin Chen,1 Na Zhou,1 Hui Liu,1 Shiling Dong,1 Hong-ming Hu,2 Yongbin Mou11Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 2Laboratory of Cancer Immunobiology, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center, Portland, OR, USA; 3Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, China*These authors contributed equally to this workBackground: The aim of this study was to explore the feasibility of delivering tumor antigens and enhancing the antigen cross-presentation of dendritic cells (DCs) by aluminum hydroxide nanoparticle with polyethyleneimine (PEI) modification (LV@HPA/PEI). Materials and methods: The LV@HPA nanoparticles were modified by PEI first, then the influence of LV@HPA/PEI on DCs was examined. The distinct expression of ovalbumin (OVA) protein transported into DCs by LV@HPA/PEI was observed by flow cytometry and Western blot. The biocompatibility of LV@HPA/PEI, maturity and antigen cross-presentation of DCs was observed in vitro. Tumor derived autophagosomes (DRibbles) combined with LV@HPA/PEI were loaded into DCs, and DC vaccines were used to immunize mice. The percentage of CD3+CD8+IFN-γ+ T cells in immunized mice was determined by flow cytometry. Additionally, the functional properties of the LV@HPA/PEI-DRibble-DCs vaccine were examined in vivo in PancO2 tumor-bearing mice.Results: In our study, we described how LV@HPA/PEI can be a functionalized antigen delivery system with notable antigen transport effect and negligible cytotoxicity. It was found that LV@HPA/PEI could be easily internalized into DCs to assist antigen release into the cytoplasm. In addition, DCs matured gradually after loading with LV@HPA/PEI-OVA, which increased significantly the cytokine IL-12 secretion and expression of surface molecules CD80 and CD86. Interestingly, DCs loaded with LV@HPA/PEI-DRibbles could promote the activation of tumor-specific T cells both in murine and in human T cells. In the following in vivo experiments, the vaccine of LV@HPA/PEI-DRibble-DCs significantly inhibited tumor growth and improved the survival rate of the PancO2 tumor-bearing mice.Conclusion: We established a high-performance anti-tumor vaccine of DCs loaded with LV@HPA/PEI nanoparticles and tumor-associated antigens in autophagosomes (DRibbles), which could serve as a therapeutic strategy in cancer immunotherapy.Keywords: aluminum hydroxide, antigen delivery, DRibbles, nano-adjuvant, cancer immunotherapy, autophagosome
format	article
author	Dong H Wen ZF Chen L Zhou N Liu H Dong S Hu HM Mou YB
author_facet	Dong H Wen ZF Chen L Zhou N Liu H Dong S Hu HM Mou YB
author_sort	Dong H
title	Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells
title_short	Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells
title_full	Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells
title_fullStr	Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells
title_full_unstemmed	Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells
title_sort	polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/e7e10d8c0b9a405a9f387b73e3cd389b
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Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells

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