Cargando…
Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC
BACKGROUND: 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 nov...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457883/ https://www.ncbi.nlm.nih.gov/pubmed/32922011 http://dx.doi.org/10.2147/IJN.S258906 |
_version_ | 1783576087733731328 |
---|---|
author | Kong, Liang Zhang, Shi-meng Chu, Jia-hao Liu, Xin-ze Zhang, Lu He, Si-yu Yang, Si-min Ju, Rui-jun Li, Xue-tao |
author_facet | Kong, Liang Zhang, Shi-meng Chu, Jia-hao Liu, Xin-ze Zhang, Lu He, Si-yu Yang, Si-min Ju, Rui-jun Li, Xue-tao |
author_sort | Kong, Liang |
collection | PubMed |
description | BACKGROUND: 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-PEG(2000)-MAL and CPP-PVGLIG-PEG(5000), 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. |
format | Online Article Text |
id | pubmed-7457883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-74578832020-09-11 Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC Kong, Liang Zhang, Shi-meng Chu, Jia-hao Liu, Xin-ze Zhang, Lu He, Si-yu Yang, Si-min Ju, Rui-jun Li, Xue-tao Int J Nanomedicine Original Research BACKGROUND: 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-PEG(2000)-MAL and CPP-PVGLIG-PEG(5000), 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. Dove 2020-08-25 /pmc/articles/PMC7457883/ /pubmed/32922011 http://dx.doi.org/10.2147/IJN.S258906 Text en © 2020 Kong et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Kong, Liang Zhang, Shi-meng Chu, Jia-hao Liu, Xin-ze Zhang, Lu He, Si-yu Yang, Si-min Ju, Rui-jun Li, Xue-tao Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC |
title | 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_short | 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 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457883/ https://www.ncbi.nlm.nih.gov/pubmed/32922011 http://dx.doi.org/10.2147/IJN.S258906 |
work_keys_str_mv | AT kongliang tumormicroenvironmentalresponsiveliposomessimultaneouslyencapsulatingbiologicalandchemotherapeuticdrugsforenhancingantitumorefficacyofnsclc AT zhangshimeng tumormicroenvironmentalresponsiveliposomessimultaneouslyencapsulatingbiologicalandchemotherapeuticdrugsforenhancingantitumorefficacyofnsclc AT chujiahao tumormicroenvironmentalresponsiveliposomessimultaneouslyencapsulatingbiologicalandchemotherapeuticdrugsforenhancingantitumorefficacyofnsclc AT liuxinze tumormicroenvironmentalresponsiveliposomessimultaneouslyencapsulatingbiologicalandchemotherapeuticdrugsforenhancingantitumorefficacyofnsclc AT zhanglu tumormicroenvironmentalresponsiveliposomessimultaneouslyencapsulatingbiologicalandchemotherapeuticdrugsforenhancingantitumorefficacyofnsclc AT hesiyu tumormicroenvironmentalresponsiveliposomessimultaneouslyencapsulatingbiologicalandchemotherapeuticdrugsforenhancingantitumorefficacyofnsclc AT yangsimin tumormicroenvironmentalresponsiveliposomessimultaneouslyencapsulatingbiologicalandchemotherapeuticdrugsforenhancingantitumorefficacyofnsclc AT juruijun tumormicroenvironmentalresponsiveliposomessimultaneouslyencapsulatingbiologicalandchemotherapeuticdrugsforenhancingantitumorefficacyofnsclc AT lixuetao tumormicroenvironmentalresponsiveliposomessimultaneouslyencapsulatingbiologicalandchemotherapeuticdrugsforenhancingantitumorefficacyofnsclc |