Immunotherapy of Tumor RNA-Loaded Lipid Nanoparticles Against Hepatocellular Carcinoma

Yake Zhang,1,2,* Fangyuan Xie,3,* You Yin,4,* Qin Zhang,1,* Hong Jin,5 Yan Wu,6 Liying Pang,7 Jun Li,2 Jie Gao1,2 1Institute of Translational Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China; 2Laboratory of Drug Discovery and Design, School of Pharmacy, Liaocheng...

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Autores principales:	Zhang Y, Xie F, Yin Y, Zhang Q, Jin H, Wu Y, Pang L, Li J, Gao J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	rna lipid nanoparticles tumor vaccine dendritic cells cancer immunotherapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/72dcbe4211124378bac0b859fc134551
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id	oai:doaj.org-article:72dcbe4211124378bac0b859fc134551
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	rna lipid nanoparticles tumor vaccine dendritic cells cancer immunotherapy Medicine (General) R5-920
spellingShingle	rna lipid nanoparticles tumor vaccine dendritic cells cancer immunotherapy Medicine (General) R5-920 Zhang Y Xie F Yin Y Zhang Q Jin H Wu Y Pang L Li J Gao J Immunotherapy of Tumor RNA-Loaded Lipid Nanoparticles Against Hepatocellular Carcinoma
description	Yake Zhang,1,2,* Fangyuan Xie,3,* You Yin,4,* Qin Zhang,1,* Hong Jin,5 Yan Wu,6 Liying Pang,7 Jun Li,2 Jie Gao1,2 1Institute of Translational Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China; 2Laboratory of Drug Discovery and Design, School of Pharmacy, Liaocheng University, Liaocheng, 252000, People’s Republic of China; 3Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China; 4Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China; 5Department of Laboratory Medicine, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, 157011, People’s Republic of China; 6Heilongjiang Key Laboratory of Anti-Fibrosis Biotherapy, Mudanjiang Medical College, Mudanjiang, 157011, People’s Republic of China; 7The First Clinical Medical College of Mudanjiang Medical College, Mudanjiang, 157011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie GaoInstitute of Translational Medicine, Shanghai University, Shanghai, 200444, People’s Republic of ChinaTel/Fax + 86-0577-88816381Email gaojiehighclea@163.comJun LiLaboratory of Drug Discovery and Design, School of Pharmacy, Liaocheng University, Liaocheng, 252000, People’s Republic of ChinaTel/Fax + 86-0577-88816381Email lijun1982@lcu.edu.cnPurpose: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Most current therapeutic strategies primarily include localized treatment, lacking effective systemic strategies. Meanwhile, recent studies have suggested that RNA vaccines can effectively activate antigen-presenting cells (APCs) and lymphocytes to produce a strong systemic immune response and inhibit tumor growth. However, tumor vaccines loaded with a single tumor antigen may induce immunosuppression and immune evasion, while identifying tumor-specific antigens can require expensive and laborious procedures. Therefore, the use of whole tumor cell antigens are currently considered to be promising, potentially effective, methods. Previously, we developed a targeted liposome-polycation-DNA (LPD) complex nanoparticle that possess a small size, high RNA encapsulation efficiency, and superior serum stability. These particles were found to successfully deliver RNA to tumor sites. In the current study, we encapsulated total tumor-derived RNA in lipid nanoparticles (LNPs) to target dendritic cells (DCs) to incite expeditious and robust anti-tumor immunity.Methods: Total tumor-derived RNA was extracted from liver cancer cells (Hepa1-6 cells). LNPs loaded with tumor RNA were then prepared thin-film hydration method. The ability of RNA LNPs to induce DC maturation, cytotoxicity, and anti-tumor activity, was investigated in vitro and in vivo.Results: The average particle size of LNPs and RNA LNPs was 102.22 ± 4.05 nm and 209.68 ± 6.14 nm, respectively, while the zeta potential was 29.97 ± 0.61 mV and 42.03 ± 0.42 mV, respectively. Both LNPs and RNA LNP vaccines exhibited good distribution and stability. In vitro, RNA LNP vaccines were capable of promoting DC maturation and inducing T lymphocytes to kill Hepa1-6 cells. In vivo, RNA LNP vaccines effectively prevent and inhibit HCC growth.Conclusion: RNA LNPs may serve as an effective antigen specific vaccine to induce anti-tumor immunity for HCC.Keywords: RNA lipid nanoparticles, tumor vaccine, dendritic cells, cancer immunotherapy
format	article
author	Zhang Y Xie F Yin Y Zhang Q Jin H Wu Y Pang L Li J Gao J
author_facet	Zhang Y Xie F Yin Y Zhang Q Jin H Wu Y Pang L Li J Gao J
author_sort	Zhang Y
title	Immunotherapy of Tumor RNA-Loaded Lipid Nanoparticles Against Hepatocellular Carcinoma
title_short	Immunotherapy of Tumor RNA-Loaded Lipid Nanoparticles Against Hepatocellular Carcinoma
title_full	Immunotherapy of Tumor RNA-Loaded Lipid Nanoparticles Against Hepatocellular Carcinoma
title_fullStr	Immunotherapy of Tumor RNA-Loaded Lipid Nanoparticles Against Hepatocellular Carcinoma
title_full_unstemmed	Immunotherapy of Tumor RNA-Loaded Lipid Nanoparticles Against Hepatocellular Carcinoma
title_sort	immunotherapy of tumor rna-loaded lipid nanoparticles against hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/72dcbe4211124378bac0b859fc134551
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spelling	oai:doaj.org-article:72dcbe4211124378bac0b859fc1345512021-12-02T14:40:32ZImmunotherapy of Tumor RNA-Loaded Lipid Nanoparticles Against Hepatocellular Carcinoma1178-2013https://doaj.org/article/72dcbe4211124378bac0b859fc1345512021-02-01T00:00:00Zhttps://www.dovepress.com/immunotherapy-of-tumor-rna-loaded-lipid-nanoparticles-against-hepatoce-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yake Zhang,1,2,* Fangyuan Xie,3,* You Yin,4,* Qin Zhang,1,* Hong Jin,5 Yan Wu,6 Liying Pang,7 Jun Li,2 Jie Gao1,2 1Institute of Translational Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China; 2Laboratory of Drug Discovery and Design, School of Pharmacy, Liaocheng University, Liaocheng, 252000, People’s Republic of China; 3Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China; 4Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China; 5Department of Laboratory Medicine, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, 157011, People’s Republic of China; 6Heilongjiang Key Laboratory of Anti-Fibrosis Biotherapy, Mudanjiang Medical College, Mudanjiang, 157011, People’s Republic of China; 7The First Clinical Medical College of Mudanjiang Medical College, Mudanjiang, 157011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie GaoInstitute of Translational Medicine, Shanghai University, Shanghai, 200444, People’s Republic of ChinaTel/Fax + 86-0577-88816381Email gaojiehighclea@163.comJun LiLaboratory of Drug Discovery and Design, School of Pharmacy, Liaocheng University, Liaocheng, 252000, People’s Republic of ChinaTel/Fax + 86-0577-88816381Email lijun1982@lcu.edu.cnPurpose: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Most current therapeutic strategies primarily include localized treatment, lacking effective systemic strategies. Meanwhile, recent studies have suggested that RNA vaccines can effectively activate antigen-presenting cells (APCs) and lymphocytes to produce a strong systemic immune response and inhibit tumor growth. However, tumor vaccines loaded with a single tumor antigen may induce immunosuppression and immune evasion, while identifying tumor-specific antigens can require expensive and laborious procedures. Therefore, the use of whole tumor cell antigens are currently considered to be promising, potentially effective, methods. Previously, we developed a targeted liposome-polycation-DNA (LPD) complex nanoparticle that possess a small size, high RNA encapsulation efficiency, and superior serum stability. These particles were found to successfully deliver RNA to tumor sites. In the current study, we encapsulated total tumor-derived RNA in lipid nanoparticles (LNPs) to target dendritic cells (DCs) to incite expeditious and robust anti-tumor immunity.Methods: Total tumor-derived RNA was extracted from liver cancer cells (Hepa1-6 cells). LNPs loaded with tumor RNA were then prepared thin-film hydration method. The ability of RNA LNPs to induce DC maturation, cytotoxicity, and anti-tumor activity, was investigated in vitro and in vivo.Results: The average particle size of LNPs and RNA LNPs was 102.22 ± 4.05 nm and 209.68 ± 6.14 nm, respectively, while the zeta potential was 29.97 ± 0.61 mV and 42.03 ± 0.42 mV, respectively. Both LNPs and RNA LNP vaccines exhibited good distribution and stability. In vitro, RNA LNP vaccines were capable of promoting DC maturation and inducing T lymphocytes to kill Hepa1-6 cells. In vivo, RNA LNP vaccines effectively prevent and inhibit HCC growth.Conclusion: RNA LNPs may serve as an effective antigen specific vaccine to induce anti-tumor immunity for HCC.Keywords: RNA lipid nanoparticles, tumor vaccine, dendritic cells, cancer immunotherapyZhang YXie FYin YZhang QJin HWu YPang LLi JGao JDove Medical Pressarticlerna lipid nanoparticlestumor vaccinedendritic cellscancer immunotherapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1553-1564 (2021)

Immunotherapy of Tumor RNA-Loaded Lipid Nanoparticles Against Hepatocellular Carcinoma

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