Cargando…

Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis

Metastasis is a major cause of chemotherapeutic failure and death. Degradation of a specific component of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) affects the physical barrier of the tumor microenvironment (TME) and induces metastasis. Here, lysolipid-containing thermosensi...

Descripción completa

Detalles Bibliográficos
Autores principales: Lyu, Yaqi, Xiao, Qingqing, Yin, Lifang, Yang, Lei, He, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799847/
https://www.ncbi.nlm.nih.gov/pubmed/31637006
http://dx.doi.org/10.1038/s41392-019-0054-9
_version_ 1783460379665367040
author Lyu, Yaqi
Xiao, Qingqing
Yin, Lifang
Yang, Lei
He, Wei
author_facet Lyu, Yaqi
Xiao, Qingqing
Yin, Lifang
Yang, Lei
He, Wei
author_sort Lyu, Yaqi
collection PubMed
description Metastasis is a major cause of chemotherapeutic failure and death. Degradation of a specific component of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) affects the physical barrier of the tumor microenvironment (TME) and induces metastasis. Here, lysolipid-containing thermosensitive liposomes (LTSLs) were prepared to deliver an MMP inhibitor, marimastat (MATT), to the TME to inhibit MMP activity and expression. LTSLs rapidly released their payloads at 42 °C. Compared with the saline control, MATT-LTSLs exhibited enhanced accumulation in the tumor and a 20-fold decrease in tumor growth in 4T1 tumor-bearing mice; moreover, MATT-LTSLs reduced MMP-2 and MMP-9 activity by 50% and 43%, respectively, and downregulated MMP-2 and MMP-9 expression in vivo by 30% and 43%, respectively. Most importantly, MATT-LTSL treatment caused a 7-fold decrease in metastatic lung nodules and a 6-fold reduction in microvessels inside the tumor. We believe this study provides an effective approach for the suppression of metastasis, and the use of a cytotoxic agent in combination with MATT is a potential strategy for metastatic cancer treatment.
format Online
Article
Text
id pubmed-6799847
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-67998472019-10-21 Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis Lyu, Yaqi Xiao, Qingqing Yin, Lifang Yang, Lei He, Wei Signal Transduct Target Ther Article Metastasis is a major cause of chemotherapeutic failure and death. Degradation of a specific component of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) affects the physical barrier of the tumor microenvironment (TME) and induces metastasis. Here, lysolipid-containing thermosensitive liposomes (LTSLs) were prepared to deliver an MMP inhibitor, marimastat (MATT), to the TME to inhibit MMP activity and expression. LTSLs rapidly released their payloads at 42 °C. Compared with the saline control, MATT-LTSLs exhibited enhanced accumulation in the tumor and a 20-fold decrease in tumor growth in 4T1 tumor-bearing mice; moreover, MATT-LTSLs reduced MMP-2 and MMP-9 activity by 50% and 43%, respectively, and downregulated MMP-2 and MMP-9 expression in vivo by 30% and 43%, respectively. Most importantly, MATT-LTSL treatment caused a 7-fold decrease in metastatic lung nodules and a 6-fold reduction in microvessels inside the tumor. We believe this study provides an effective approach for the suppression of metastasis, and the use of a cytotoxic agent in combination with MATT is a potential strategy for metastatic cancer treatment. Nature Publishing Group UK 2019-08-09 /pmc/articles/PMC6799847/ /pubmed/31637006 http://dx.doi.org/10.1038/s41392-019-0054-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lyu, Yaqi
Xiao, Qingqing
Yin, Lifang
Yang, Lei
He, Wei
Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis
title Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis
title_full Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis
title_fullStr Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis
title_full_unstemmed Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis
title_short Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis
title_sort potent delivery of an mmp inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799847/
https://www.ncbi.nlm.nih.gov/pubmed/31637006
http://dx.doi.org/10.1038/s41392-019-0054-9
work_keys_str_mv AT lyuyaqi potentdeliveryofanmmpinhibitortothetumormicroenvironmentwiththermosensitiveliposomesforthesuppressionofmetastasisandangiogenesis
AT xiaoqingqing potentdeliveryofanmmpinhibitortothetumormicroenvironmentwiththermosensitiveliposomesforthesuppressionofmetastasisandangiogenesis
AT yinlifang potentdeliveryofanmmpinhibitortothetumormicroenvironmentwiththermosensitiveliposomesforthesuppressionofmetastasisandangiogenesis
AT yanglei potentdeliveryofanmmpinhibitortothetumormicroenvironmentwiththermosensitiveliposomesforthesuppressionofmetastasisandangiogenesis
AT hewei potentdeliveryofanmmpinhibitortothetumormicroenvironmentwiththermosensitiveliposomesforthesuppressionofmetastasisandangiogenesis