In vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice

Ziqiang Ding,1,2,* Dujin Wang,1,2,* Wei Shi,2,3,* Xiaomei Yang,2,3 Siliang Duan,2 Fengzhen Mo,2 Xiaoqiong Hou,2,3 Aiqun Liu,2 Xiaoling Lu2,4 1National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, People&rsqu...

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Autores principales:	Ding Z, Wang D, Shi W, Yang X, Duan S, Mo F, Hou X, Liu A, Lu X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	targeted drug delivery liver cancer treatment msn-based vehicles doxorubicin tissue- and nuclei-specific targeting Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5c8ac77a16ed4cadb99026f8060a82fe
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spelling	oai:doaj.org-article:5c8ac77a16ed4cadb99026f8060a82fe2021-12-02T11:06:48ZIn vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice1178-2013https://doaj.org/article/5c8ac77a16ed4cadb99026f8060a82fe2020-10-01T00:00:00Zhttps://www.dovepress.com/in-vivo-targeting-of-liver-cancer-with-tissue--and-nuclei-specific-mes-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ziqiang Ding,1,2,* Dujin Wang,1,2,* Wei Shi,2,3,* Xiaomei Yang,2,3 Siliang Duan,2 Fengzhen Mo,2 Xiaoqiong Hou,2,3 Aiqun Liu,2 Xiaoling Lu2,4 1National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2International Nanobody Research Center of Guangxi, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 3School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 4College of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoling LuInternational Nanobody Research Center of Guangxi, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of ChinaTel/Fax +86 771-2387 518Email luxiaoling@gxmu.edu.cnPurpose: Cancer tissue-specific and nuclei-targeted drug delivery is ideal for the delivery of chemotherapy. However, it has only been achieved in in vitro studies mainly due to low efficiency in vivo. In this study, we aimed to establish an efficient dual-targeted system that targets liver cancer tissue as well as the nuclei of cancer cells in vivo.Methods: We first synthesized TAT peptide (TATp)-mesoporous silica nanoparticle (MSN) complex (TATp-MSN) and generated liposomes that carried liver cancer-specific aptamer TLS11a (TLS11a-LB). We then generated the drug TLS11a-LB@TATp-MSN/doxorubicin (DOX) by mixing TLS11a-LB and DOX-loaded TATp-MSN. After physical and chemical characterization of the nanoparticles, DOX release from these formulations was evaluated at pH 5.0 and 7.4. Furthermore, we also evaluated nuclear localization and cytotoxicity of the drug in H22 cells in vitro and investigated the liver cancer targeting and antitumor activities of the nano-drug in vivo using a H22 tumor-bearing mice model.Results: TLS11a-LB@TATp-MSN/DOX and its controls were confirmed as nano-drugs (< 100 nm) using transmission electron microscopy (TEM). The DOX release rate of TLS11a-LB@TATp-MSN/DOX was significantly faster at pH 5.0 than at pH 7.4. TLS11a-LB@TATp-MSN/DOX effectively targeted the nuclei of H22 cells and released DOX with a higher efficiency than that of the control groups. In addition, TLS11a-LB@TATp-MSN/DOX exhibited slight cytotoxicity, but not significantly more than controls. In vivo studies showed that TLS11a-LB@TATp-MSN accumulated in subcutaneous H22 tumors in the right axilla of BALB/c mice, reaching peak levels at 48 h after intravenous injection, respectively, and demonstrated that TLS11a-LB@TATp-MSN/DOX group enhanced tumor treatment efﬁcacy while reducing systemic side effects.Conclusion: TLS11a-LB@TATp-MSN/DOX can efficiently deliver DOX to the nuclei of liver cancer cells by dual targeting liver cancer tissue and the nuclei of the cancer cells in mice. Thus, it is a promising nano-drug for the treatment of liver cancer.Keywords: targeted drug delivery, liver cancer treatment, MSN-based vehicles, doxorubicin, tissue- and nuclei-specific targetingDing ZWang DShi WYang XDuan SMo FHou XLiu ALu XDove Medical Pressarticletargeted drug deliveryliver cancer treatmentmsn-based vehiclesdoxorubicintissue- and nuclei-specific targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 8383-8400 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	targeted drug delivery liver cancer treatment msn-based vehicles doxorubicin tissue- and nuclei-specific targeting Medicine (General) R5-920
spellingShingle	targeted drug delivery liver cancer treatment msn-based vehicles doxorubicin tissue- and nuclei-specific targeting Medicine (General) R5-920 Ding Z Wang D Shi W Yang X Duan S Mo F Hou X Liu A Lu X In vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice
description	Ziqiang Ding,1,2,* Dujin Wang,1,2,* Wei Shi,2,3,* Xiaomei Yang,2,3 Siliang Duan,2 Fengzhen Mo,2 Xiaoqiong Hou,2,3 Aiqun Liu,2 Xiaoling Lu2,4 1National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2International Nanobody Research Center of Guangxi, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 3School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 4College of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoling LuInternational Nanobody Research Center of Guangxi, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of ChinaTel/Fax +86 771-2387 518Email luxiaoling@gxmu.edu.cnPurpose: Cancer tissue-specific and nuclei-targeted drug delivery is ideal for the delivery of chemotherapy. However, it has only been achieved in in vitro studies mainly due to low efficiency in vivo. In this study, we aimed to establish an efficient dual-targeted system that targets liver cancer tissue as well as the nuclei of cancer cells in vivo.Methods: We first synthesized TAT peptide (TATp)-mesoporous silica nanoparticle (MSN) complex (TATp-MSN) and generated liposomes that carried liver cancer-specific aptamer TLS11a (TLS11a-LB). We then generated the drug TLS11a-LB@TATp-MSN/doxorubicin (DOX) by mixing TLS11a-LB and DOX-loaded TATp-MSN. After physical and chemical characterization of the nanoparticles, DOX release from these formulations was evaluated at pH 5.0 and 7.4. Furthermore, we also evaluated nuclear localization and cytotoxicity of the drug in H22 cells in vitro and investigated the liver cancer targeting and antitumor activities of the nano-drug in vivo using a H22 tumor-bearing mice model.Results: TLS11a-LB@TATp-MSN/DOX and its controls were confirmed as nano-drugs (< 100 nm) using transmission electron microscopy (TEM). The DOX release rate of TLS11a-LB@TATp-MSN/DOX was significantly faster at pH 5.0 than at pH 7.4. TLS11a-LB@TATp-MSN/DOX effectively targeted the nuclei of H22 cells and released DOX with a higher efficiency than that of the control groups. In addition, TLS11a-LB@TATp-MSN/DOX exhibited slight cytotoxicity, but not significantly more than controls. In vivo studies showed that TLS11a-LB@TATp-MSN accumulated in subcutaneous H22 tumors in the right axilla of BALB/c mice, reaching peak levels at 48 h after intravenous injection, respectively, and demonstrated that TLS11a-LB@TATp-MSN/DOX group enhanced tumor treatment efﬁcacy while reducing systemic side effects.Conclusion: TLS11a-LB@TATp-MSN/DOX can efficiently deliver DOX to the nuclei of liver cancer cells by dual targeting liver cancer tissue and the nuclei of the cancer cells in mice. Thus, it is a promising nano-drug for the treatment of liver cancer.Keywords: targeted drug delivery, liver cancer treatment, MSN-based vehicles, doxorubicin, tissue- and nuclei-specific targeting
format	article
author	Ding Z Wang D Shi W Yang X Duan S Mo F Hou X Liu A Lu X
author_facet	Ding Z Wang D Shi W Yang X Duan S Mo F Hou X Liu A Lu X
author_sort	Ding Z
title	In vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice
title_short	In vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice
title_full	In vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice
title_fullStr	In vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice
title_full_unstemmed	In vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice
title_sort	in vivo targeting of liver cancer with tissue- and nuclei-specific mesoporous silica nanoparticle-based nanocarriers in mice
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/5c8ac77a16ed4cadb99026f8060a82fe
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In vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice

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