Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity

Stimuli-responsive nanotherapeutics hold great promise in precision oncology. In this study, a facile strategy was used to develop a new class of pH-responsive micelles, which contain methoxy polyethylene glycol (mPEG) and poly(carbobenzoxy-l-glutamic acid, BLG) as amphiphilic copolymer, and β-thiop...

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Autores principales:	Qiyi Feng, Junhuai Xu, Xinyi Liu, Haibo Wang, Junjie Xiong, Kai Xiao
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	tumor microenvironment ph-responsive micelles β-thiopropionate linkage drug delivery Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/7c8547b104ad41009eed1c9800987472
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spelling	oai:doaj.org-article:7c8547b104ad41009eed1c98009874722021-12-01T14:40:58ZTargeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity1071-75441521-046410.1080/10717544.2021.2008052https://doaj.org/article/7c8547b104ad41009eed1c98009874722021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/10717544.2021.2008052https://doaj.org/toc/1071-7544https://doaj.org/toc/1521-0464Stimuli-responsive nanotherapeutics hold great promise in precision oncology. In this study, a facile strategy was used to develop a new class of pH-responsive micelles, which contain methoxy polyethylene glycol (mPEG) and poly(carbobenzoxy-l-glutamic acid, BLG) as amphiphilic copolymer, and β-thiopropionate as acid-labile linkage. The mPEG-S-PBLG copolymer was synthesized through one-step ring-opening polymerization (ROP) and thiol-ene click reaction, and was able to efficiently encapsulate doxorubicin (DOX) to form micelles. The physicochemical characteristics, cellular uptake, tumor targeting, and anti-tumor efficacy of DOX-loaded micelles were investigated. DOX-loaded micelles were stable under physiological conditions and disintegrated under acidic conditions. DOX-loaded micelles can be internalized into cancer cells and release drugs in response to low pH in endosomes/lysosomes, resulting in cell death. Furthermore, the micellar formulation significantly prolonged the blood circulation, reduced the cardiac distribution, and selectively delivered more drugs to tumor tissue. Finally, compared with free DOX, DOX-loaded micelles significantly improved the anti-tumor efficacy and reduced systemic and cardiac toxicity in two different tumor xenograft models. These results suggest that mPEG-S-PBLG micelles have translational potential in the precise delivery of anti-cancer drugs.Qiyi FengJunhuai XuXinyi LiuHaibo WangJunjie XiongKai XiaoTaylor & Francis Grouparticletumor microenvironmentph-responsivemicellesβ-thiopropionate linkagedrug deliveryTherapeutics. PharmacologyRM1-950ENDrug Delivery, Vol 28, Iss 1, Pp 2495-2509 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tumor microenvironment ph-responsive micelles β-thiopropionate linkage drug delivery Therapeutics. Pharmacology RM1-950
spellingShingle	tumor microenvironment ph-responsive micelles β-thiopropionate linkage drug delivery Therapeutics. Pharmacology RM1-950 Qiyi Feng Junhuai Xu Xinyi Liu Haibo Wang Junjie Xiong Kai Xiao Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity
description	Stimuli-responsive nanotherapeutics hold great promise in precision oncology. In this study, a facile strategy was used to develop a new class of pH-responsive micelles, which contain methoxy polyethylene glycol (mPEG) and poly(carbobenzoxy-l-glutamic acid, BLG) as amphiphilic copolymer, and β-thiopropionate as acid-labile linkage. The mPEG-S-PBLG copolymer was synthesized through one-step ring-opening polymerization (ROP) and thiol-ene click reaction, and was able to efficiently encapsulate doxorubicin (DOX) to form micelles. The physicochemical characteristics, cellular uptake, tumor targeting, and anti-tumor efficacy of DOX-loaded micelles were investigated. DOX-loaded micelles were stable under physiological conditions and disintegrated under acidic conditions. DOX-loaded micelles can be internalized into cancer cells and release drugs in response to low pH in endosomes/lysosomes, resulting in cell death. Furthermore, the micellar formulation significantly prolonged the blood circulation, reduced the cardiac distribution, and selectively delivered more drugs to tumor tissue. Finally, compared with free DOX, DOX-loaded micelles significantly improved the anti-tumor efficacy and reduced systemic and cardiac toxicity in two different tumor xenograft models. These results suggest that mPEG-S-PBLG micelles have translational potential in the precise delivery of anti-cancer drugs.
format	article
author	Qiyi Feng Junhuai Xu Xinyi Liu Haibo Wang Junjie Xiong Kai Xiao
author_facet	Qiyi Feng Junhuai Xu Xinyi Liu Haibo Wang Junjie Xiong Kai Xiao
author_sort	Qiyi Feng
title	Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity
title_short	Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity
title_full	Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity
title_fullStr	Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity
title_full_unstemmed	Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity
title_sort	targeted delivery by ph-responsive mpeg-s-pblg micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/7c8547b104ad41009eed1c9800987472
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Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity

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