Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC

Liang Kong,1 Shi-meng Zhang,2 Jia-hao Chu,3 Xin-ze Liu,1 Lu Zhang,1 Si-yu He,1 Si-min Yang,3 Rui-jun Ju,3 Xue-tao Li1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People’s Republic of China; 2Department of Neurology, Linyi People’s Hosp...

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Autores principales:	Kong L, Zhang S, Chu J, Liu X, Zhang L, He S, Yang S, Ju R, Li X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	vinorelbine dioscin non-small cell lung cancer multi-functional liposomes tumor microenvironment mmp2 enzymes Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/55806ad6f7984f20a4b727301c96af72
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spelling	oai:doaj.org-article:55806ad6f7984f20a4b727301c96af722021-12-02T13:20:29ZTumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC1178-2013https://doaj.org/article/55806ad6f7984f20a4b727301c96af722020-08-01T00:00:00Zhttps://www.dovepress.com/tumor-microenvironmental-responsive-liposomes-simultaneously-encapsula-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Liang Kong,1 Shi-meng Zhang,2 Jia-hao Chu,3 Xin-ze Liu,1 Lu Zhang,1 Si-yu He,1 Si-min Yang,3 Rui-jun Ju,3 Xue-tao Li1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People’s Republic of China; 2Department of Neurology, Linyi People’s Hospital, Linyi 276003, People’s Republic of China; 3Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, People’s Republic of ChinaCorrespondence: Xue-tao LiSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shengming 1 Road 77, Double D Port, Dalian 116600, People’s Republic of ChinaTel +86411 8589 0170Fax +86411 8589 0128Email lixuetao1979@163.comRui-jun JuDepartment of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Qingyuan North Road 19, Beijing 102617, People’s Republic of ChinaTel +8610 8129 2387Fax +8610 8129 2124Email juruijun@bipt.edu.cnBackground: Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse.Purpose: The objective of this study was to construct a novel CPP (mmp) modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG2000-MAL and CPP-PVGLIG-PEG5000, to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration.Methods and Results: The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP (mmp) modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP (mmp) modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency.Conclusion: CPP (mmp) modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.Keywords: vinorelbine, dioscin, non-small cell lung cancer, multi-functional liposomes, tumor microenvironment, MMP2 enzymesKong LZhang SChu JLiu XZhang LHe SYang SJu RLi XDove Medical Pressarticlevinorelbinedioscinnon-small cell lung cancermulti-functional liposomestumor microenvironmentmmp2 enzymesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 6451-6468 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	vinorelbine dioscin non-small cell lung cancer multi-functional liposomes tumor microenvironment mmp2 enzymes Medicine (General) R5-920
spellingShingle	vinorelbine dioscin non-small cell lung cancer multi-functional liposomes tumor microenvironment mmp2 enzymes Medicine (General) R5-920 Kong L Zhang S Chu J Liu X Zhang L He S Yang S Ju R Li X Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC
description	Liang Kong,1 Shi-meng Zhang,2 Jia-hao Chu,3 Xin-ze Liu,1 Lu Zhang,1 Si-yu He,1 Si-min Yang,3 Rui-jun Ju,3 Xue-tao Li1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People’s Republic of China; 2Department of Neurology, Linyi People’s Hospital, Linyi 276003, People’s Republic of China; 3Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, People’s Republic of ChinaCorrespondence: Xue-tao LiSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shengming 1 Road 77, Double D Port, Dalian 116600, People’s Republic of ChinaTel +86411 8589 0170Fax +86411 8589 0128Email lixuetao1979@163.comRui-jun JuDepartment of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Qingyuan North Road 19, Beijing 102617, People’s Republic of ChinaTel +8610 8129 2387Fax +8610 8129 2124Email juruijun@bipt.edu.cnBackground: Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse.Purpose: The objective of this study was to construct a novel CPP (mmp) modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG2000-MAL and CPP-PVGLIG-PEG5000, to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration.Methods and Results: The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP (mmp) modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP (mmp) modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency.Conclusion: CPP (mmp) modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.Keywords: vinorelbine, dioscin, non-small cell lung cancer, multi-functional liposomes, tumor microenvironment, MMP2 enzymes
format	article
author	Kong L Zhang S Chu J Liu X Zhang L He S Yang S Ju R Li X
author_facet	Kong L Zhang S Chu J Liu X Zhang L He S Yang S Ju R Li X
author_sort	Kong L
title	Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC
title_short	Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC
title_full	Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC
title_fullStr	Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC
title_full_unstemmed	Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC
title_sort	tumor microenvironmental responsive liposomes simultaneously encapsulating biological and chemotherapeutic drugs for enhancing antitumor efficacy of nsclc
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/55806ad6f7984f20a4b727301c96af72
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Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC

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