Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex

Xin Xin, Wei Liu, Zhe-Ao Zhang, Ying Han, Ling-Ling Qi, Ying-Ying Zhang, Xin-Tong Zhang, Hong-Xia Duan, Li-Qing Chen, Ming-Ji Jin, Qi-Ming Wang, Zhong-Gao Gao, Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia M...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xin X, Liu W, Zhang ZA, Han Y, Qi LL, Zhang YY, Zhang XT, Duan HX, Chen LQ, Jin MJ, Wang QM, Gao ZG, Huang W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	glioma blood-brain barrier rvg15 liposome paclitaxel Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8d0940b602ed46a7a0ce40292cb85199
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8d0940b602ed46a7a0ce40292cb85199
record_format	dspace
spelling	oai:doaj.org-article:8d0940b602ed46a7a0ce40292cb851992021-12-02T16:39:58ZEfficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex1178-2013https://doaj.org/article/8d0940b602ed46a7a0ce40292cb851992021-08-01T00:00:00Zhttps://www.dovepress.com/efficient-anti-glioma-therapy-through-the-brain-targeted-rvg15-modifie-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Xin Xin, Wei Liu, Zhe-Ao Zhang, Ying Han, Ling-Ling Qi, Ying-Ying Zhang, Xin-Tong Zhang, Hong-Xia Duan, Li-Qing Chen, Ming-Ji Jin, Qi-Ming Wang, Zhong-Gao Gao, Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of ChinaCorrespondence: Zhong-Gao Gao; Wei HuangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, People’s Republic of ChinaTel +86-10-63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood–brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly.Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and − 15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect.Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.Keywords: glioma, blood–brain barrier, RVG15, liposome, paclitaxelXin XLiu WZhang ZAHan YQi LLZhang YYZhang XTDuan HXChen LQJin MJWang QMGao ZGHuang WDove Medical Pressarticlegliomablood-brain barrierrvg15liposomepaclitaxelMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 5755-5776 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioma blood-brain barrier rvg15 liposome paclitaxel Medicine (General) R5-920
spellingShingle	glioma blood-brain barrier rvg15 liposome paclitaxel Medicine (General) R5-920 Xin X Liu W Zhang ZA Han Y Qi LL Zhang YY Zhang XT Duan HX Chen LQ Jin MJ Wang QM Gao ZG Huang W Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex
description	Xin Xin, Wei Liu, Zhe-Ao Zhang, Ying Han, Ling-Ling Qi, Ying-Ying Zhang, Xin-Tong Zhang, Hong-Xia Duan, Li-Qing Chen, Ming-Ji Jin, Qi-Ming Wang, Zhong-Gao Gao, Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of ChinaCorrespondence: Zhong-Gao Gao; Wei HuangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, People’s Republic of ChinaTel +86-10-63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood–brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly.Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and − 15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect.Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.Keywords: glioma, blood–brain barrier, RVG15, liposome, paclitaxel
format	article
author	Xin X Liu W Zhang ZA Han Y Qi LL Zhang YY Zhang XT Duan HX Chen LQ Jin MJ Wang QM Gao ZG Huang W
author_facet	Xin X Liu W Zhang ZA Han Y Qi LL Zhang YY Zhang XT Duan HX Chen LQ Jin MJ Wang QM Gao ZG Huang W
author_sort	Xin X
title	Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex
title_short	Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex
title_full	Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex
title_fullStr	Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex
title_full_unstemmed	Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex
title_sort	efficient anti-glioma therapy through the brain-targeted rvg15-modified liposomes loading paclitaxel-cholesterol complex
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/8d0940b602ed46a7a0ce40292cb85199
work_keys_str_mv	AT xinx efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT liuw efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT zhangza efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT hany efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT qill efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT zhangyy efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT zhangxt efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT duanhx efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT chenlq efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT jinmj efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT wangqm efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT gaozg efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex AT huangw efficientantigliomatherapythroughthebraintargetedrvg15modifiedliposomesloadingpaclitaxelcholesterolcomplex
_version_	1718383584858865664

Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex

Ejemplares similares