Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile

Lei Zhang,1,* Fengjun He,1,* Lina Gao,1 Minghui Cong,1 Juan Sun,2 Jialu Xu,2 Yutong Wang,2 Yang Hu,1 Sajid Asghar,3 Lihong Hu,1,2 Hongzhi Qiao1,2,4 1Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Repub...

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Autores principales:	Zhang L, He F, Gao L, Cong M, Sun J, Xu J, Wang Y, Hu Y, Asghar S, Hu L, Qiao H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	exosome exosome-like nanovesicles asparagus cochinchinensis engineering exosome antitumor Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6da99c29508d40c0a36909787c92e6a7
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spelling	oai:doaj.org-article:6da99c29508d40c0a36909787c92e6a72021-12-02T14:40:32ZEngineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile1178-2013https://doaj.org/article/6da99c29508d40c0a36909787c92e6a72021-02-01T00:00:00Zhttps://www.dovepress.com/engineering-exosome-like-nanovesicles-derived-from-asparagus-cochinchi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lei Zhang,1,* Fengjun He,1,* Lina Gao,1 Minghui Cong,1 Juan Sun,2 Jialu Xu,2 Yutong Wang,2 Yang Hu,1 Sajid Asghar,3 Lihong Hu,1,2 Hongzhi Qiao1,2,4 1Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 3Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan; 4Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongzhi Qiao; Lihong HuSchool of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210023, People’s Republic of ChinaEmail qiaohz@njucm.edu.cn; lhhu@njucm.edu.cnBackground: Exosomes are a type of membrane vesicles secreted by living cells. Recent studies suggest exosome-like nanovesicles (ELNVs) from fruits and vegetables are involved in tissue renewal process and functional regulation against inflammatory diseases or cancers. However, there are few reports on ELNVs derived from medicinal plants.Methods: ELNVs derived from Asparagus cochinchinensis (Lour.) Merr. (ACNVs) were isolated and characterized. Cytotoxicity, antiproliferative and apoptosis-inducing capacity of ACNVs against hepatoma carcinoma cell were assessed. The endocytosis mechanism of ACNVs was evaluated on Hep G2 cells in the presence of different endocytosis inhibitors. In vivo distribution of ACNVs was detected in healthy and tumor-bearing mice after scavenger receptors (SRs) blockade. PEG engineering of ACNVs was achieved through optimizing the pharmacokinetic profiles. In vivo antitumor activity and toxicity were evaluated in Hep G2 cell xenograft model.Results: ACNVs were isolated and purified using a differential centrifugation method accompanied by sucrose gradient ultracentrifugation. The optimized ACNVs had an average size of about 119 nm and showed a typical cup-shaped nanostructure containing lipids, proteins, and RNAs. ACNVs were found to possess specific antitumor cell proliferation activity associated with an apoptosis-inducing pathway. ACNVs could be internalized into tumor cells mainly via phagocytosis, but they were quickly cleared once entering the blood. Blocking the SRs or PEGylation decoration prolonged the blood circulation time and increased the accumulation of ACNVs in tumor sites. In vivo antitumor results showed that PEGylated ACNVs could significantly inhibit tumor growth without side effects.Conclusion: This study provides a promising functional nano platform derived from edible Asparagus cochinchinensis that can be used in antitumor therapy with negligible side effects.Keywords: exosome, exosome-like nanovesicles, Asparagus cochinchinensis, engineering exosome, antitumorZhang LHe FGao LCong MSun JXu JWang YHu YAsghar SHu LQiao HDove Medical Pressarticleexosomeexosome-like nanovesiclesasparagus cochinchinensisengineering exosomeantitumorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1575-1586 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	exosome exosome-like nanovesicles asparagus cochinchinensis engineering exosome antitumor Medicine (General) R5-920
spellingShingle	exosome exosome-like nanovesicles asparagus cochinchinensis engineering exosome antitumor Medicine (General) R5-920 Zhang L He F Gao L Cong M Sun J Xu J Wang Y Hu Y Asghar S Hu L Qiao H Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile
description	Lei Zhang,1,* Fengjun He,1,* Lina Gao,1 Minghui Cong,1 Juan Sun,2 Jialu Xu,2 Yutong Wang,2 Yang Hu,1 Sajid Asghar,3 Lihong Hu,1,2 Hongzhi Qiao1,2,4 1Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 3Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan; 4Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongzhi Qiao; Lihong HuSchool of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210023, People’s Republic of ChinaEmail qiaohz@njucm.edu.cn; lhhu@njucm.edu.cnBackground: Exosomes are a type of membrane vesicles secreted by living cells. Recent studies suggest exosome-like nanovesicles (ELNVs) from fruits and vegetables are involved in tissue renewal process and functional regulation against inflammatory diseases or cancers. However, there are few reports on ELNVs derived from medicinal plants.Methods: ELNVs derived from Asparagus cochinchinensis (Lour.) Merr. (ACNVs) were isolated and characterized. Cytotoxicity, antiproliferative and apoptosis-inducing capacity of ACNVs against hepatoma carcinoma cell were assessed. The endocytosis mechanism of ACNVs was evaluated on Hep G2 cells in the presence of different endocytosis inhibitors. In vivo distribution of ACNVs was detected in healthy and tumor-bearing mice after scavenger receptors (SRs) blockade. PEG engineering of ACNVs was achieved through optimizing the pharmacokinetic profiles. In vivo antitumor activity and toxicity were evaluated in Hep G2 cell xenograft model.Results: ACNVs were isolated and purified using a differential centrifugation method accompanied by sucrose gradient ultracentrifugation. The optimized ACNVs had an average size of about 119 nm and showed a typical cup-shaped nanostructure containing lipids, proteins, and RNAs. ACNVs were found to possess specific antitumor cell proliferation activity associated with an apoptosis-inducing pathway. ACNVs could be internalized into tumor cells mainly via phagocytosis, but they were quickly cleared once entering the blood. Blocking the SRs or PEGylation decoration prolonged the blood circulation time and increased the accumulation of ACNVs in tumor sites. In vivo antitumor results showed that PEGylated ACNVs could significantly inhibit tumor growth without side effects.Conclusion: This study provides a promising functional nano platform derived from edible Asparagus cochinchinensis that can be used in antitumor therapy with negligible side effects.Keywords: exosome, exosome-like nanovesicles, Asparagus cochinchinensis, engineering exosome, antitumor
format	article
author	Zhang L He F Gao L Cong M Sun J Xu J Wang Y Hu Y Asghar S Hu L Qiao H
author_facet	Zhang L He F Gao L Cong M Sun J Xu J Wang Y Hu Y Asghar S Hu L Qiao H
author_sort	Zhang L
title	Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile
title_short	Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile
title_full	Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile
title_fullStr	Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile
title_full_unstemmed	Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile
title_sort	engineering exosome-like nanovesicles derived from asparagus cochinchinensis can inhibit the proliferation of hepatocellular carcinoma cells with better safety profile
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/6da99c29508d40c0a36909787c92e6a7
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Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile

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