Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor

Ning Pang, Ji Li, Aning Sun, Zhenzhen Yang, Shixuan Cheng, Xian-Rong Qi Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China Background: Abnormal expression of stroma...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Pang N, Li J, Sun A, Yang Z, Cheng S, Qi XR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	two-stage therapy tumor microenvironment cancer-associated fibroblasts (CAF) tranilast docetaxel micelles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9daecfaf20a445759810fbe3dd20cf36
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9daecfaf20a445759810fbe3dd20cf36
record_format	dspace
spelling	oai:doaj.org-article:9daecfaf20a445759810fbe3dd20cf362021-12-02T00:12:50ZPrior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor1178-2013https://doaj.org/article/9daecfaf20a445759810fbe3dd20cf362018-10-01T00:00:00Zhttps://www.dovepress.com/prior-anti-cafs-break-down-the-cafs-barrier-and-improve-accumulation-o-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ning Pang, Ji Li, Aning Sun, Zhenzhen Yang, Shixuan Cheng, Xian-Rong Qi Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China Background: Abnormal expression of stromal cells and extracellular matrix in tumor stroma creates a tight barrier, leading to insufficient extravasation and penetration of therapeutic agents. Cancer-associated fibroblasts (CAFs) take on pivotal roles encouraging tumor progression.Method: To surmount the refractoriness of stroma, we constructed a multi-targeting combined scenario of anti-CAFs agent tranilast and antitumor agent docetaxel micelles (DTX-Ms). Tranilast cut down crosstalk between tumor cells and stromal cells, ameliorated the tumor microenvironment, and enhanced the antiproliferation efficacy of DTX-Ms on cancer cells.Results: Diverse experiments demonstrated that tranilast enhanced DTX-Ms’ antitumor effect in a two-stage pattern by CAFs ablation, tumor cell migration blocking, and metastasis inhibition. Along with activated CAFs decreasing in vivo, the two-stage therapy succeeded in reducing interstitial fluid pressure, normalizing microvessels, improving micelles penetration and retention, and inhibiting tumor growth and metastasis. Interestingly, tranilast alone failed to inhibit tumor growth in vivo, and it could only be used as an adjuvant medicine together with an antitumor agent.Conclusion: Our proposed two-stage therapy offers a promising strategy to enhance antitumor effects by breaking down CAFs barrier and increasing micellar delivery efficiency. Keywords: two-stage therapy, tumor microenvironment normalization, cancer-associated fibroblasts, tranilast, stromal ablationPang NLi JSun AYang ZCheng SQi XRDove Medical Pressarticletwo-stage therapytumor microenvironmentcancer-associated fibroblasts (CAF)tranilastdocetaxel micellesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 5971-5990 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	two-stage therapy tumor microenvironment cancer-associated fibroblasts (CAF) tranilast docetaxel micelles Medicine (General) R5-920
spellingShingle	two-stage therapy tumor microenvironment cancer-associated fibroblasts (CAF) tranilast docetaxel micelles Medicine (General) R5-920 Pang N Li J Sun A Yang Z Cheng S Qi XR Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor
description	Ning Pang, Ji Li, Aning Sun, Zhenzhen Yang, Shixuan Cheng, Xian-Rong Qi Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China Background: Abnormal expression of stromal cells and extracellular matrix in tumor stroma creates a tight barrier, leading to insufficient extravasation and penetration of therapeutic agents. Cancer-associated fibroblasts (CAFs) take on pivotal roles encouraging tumor progression.Method: To surmount the refractoriness of stroma, we constructed a multi-targeting combined scenario of anti-CAFs agent tranilast and antitumor agent docetaxel micelles (DTX-Ms). Tranilast cut down crosstalk between tumor cells and stromal cells, ameliorated the tumor microenvironment, and enhanced the antiproliferation efficacy of DTX-Ms on cancer cells.Results: Diverse experiments demonstrated that tranilast enhanced DTX-Ms’ antitumor effect in a two-stage pattern by CAFs ablation, tumor cell migration blocking, and metastasis inhibition. Along with activated CAFs decreasing in vivo, the two-stage therapy succeeded in reducing interstitial fluid pressure, normalizing microvessels, improving micelles penetration and retention, and inhibiting tumor growth and metastasis. Interestingly, tranilast alone failed to inhibit tumor growth in vivo, and it could only be used as an adjuvant medicine together with an antitumor agent.Conclusion: Our proposed two-stage therapy offers a promising strategy to enhance antitumor effects by breaking down CAFs barrier and increasing micellar delivery efficiency. Keywords: two-stage therapy, tumor microenvironment normalization, cancer-associated fibroblasts, tranilast, stromal ablation
format	article
author	Pang N Li J Sun A Yang Z Cheng S Qi XR
author_facet	Pang N Li J Sun A Yang Z Cheng S Qi XR
author_sort	Pang N
title	Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor
title_short	Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor
title_full	Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor
title_fullStr	Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor
title_full_unstemmed	Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor
title_sort	prior anti-cafs break down the cafs barrier and improve accumulation of docetaxel micelles in tumor
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/9daecfaf20a445759810fbe3dd20cf36
work_keys_str_mv	AT pangn prioranticafsbreakdownthecafsbarrierandimproveaccumulationofdocetaxelmicellesintumor AT lij prioranticafsbreakdownthecafsbarrierandimproveaccumulationofdocetaxelmicellesintumor AT suna prioranticafsbreakdownthecafsbarrierandimproveaccumulationofdocetaxelmicellesintumor AT yangz prioranticafsbreakdownthecafsbarrierandimproveaccumulationofdocetaxelmicellesintumor AT chengs prioranticafsbreakdownthecafsbarrierandimproveaccumulationofdocetaxelmicellesintumor AT qixr prioranticafsbreakdownthecafsbarrierandimproveaccumulationofdocetaxelmicellesintumor
_version_	1718403878772277248

Prior anti-CAFs break down the CAFs barrier and improve accumulation of docetaxel micelles in tumor

Ejemplares similares