Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel

Abstract Paclitaxel (PTX), especially albumin-bound PTX in clinical, has displayed significant inhibition of tumor growth in patients. But the systemic distribution and poor water solubility of PTX often lead to severe side effects, consequently limiting the anti-tumor efficacy. In this study, we de...

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Autores principales:	Xiaoyu Pei, Feifei Luo, Jun Zhang, Wulian Chen, Chen Jiang, Jie Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de33b223e6dd412ebdab1df4a675e07f
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spelling	oai:doaj.org-article:de33b223e6dd412ebdab1df4a675e07f2021-12-02T12:31:46ZDehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel10.1038/s41598-017-01168-72045-2322https://doaj.org/article/de33b223e6dd412ebdab1df4a675e07f2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01168-7https://doaj.org/toc/2045-2322Abstract Paclitaxel (PTX), especially albumin-bound PTX in clinical, has displayed significant inhibition of tumor growth in patients. But the systemic distribution and poor water solubility of PTX often lead to severe side effects, consequently limiting the anti-tumor efficacy. In this study, we developed a novel PTX-loaded polymeric micelle drug delivery system. These self-assembled polymeric micelles from core to outside consisted of poly L-phenylalanine (pPhe), DTSSP linked poly L-lysine (pLys), poly ethylene glycol (PEG) and dehydroascorbic acids (DHA). pPhe formed the hydrophobic core to encapsulate PTX; DTSSPs on pLys covalently cross-linked and formed disulfide bond to stabilize PTX from loss in blood circulation; PEG improved solubility to lower toxicity of PTX for its high hydrophilicity; DHA targeted tumors by specifically recognizing GLUT1 mainly expressed on tumor cells. Thus, PTX would be precisely released into tumor cells with high dose of glutathione to break disulfide bond. Moreover, these PTX-loaded polymer micelles significantly suppressed tumor cell viability, proliferation, and migration in vitro, and also greatly inhibited tumor growth and prolonged survival in tumor-bearing mice without detectable side effects. Therefore, the new drug delivery system could reduce severe side effects and enhance anti-tumor efficacy of PTX via peripheral stabilization, low toxicity and tumor targeting.Xiaoyu PeiFeifei LuoJun ZhangWulian ChenChen JiangJie LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaoyu Pei Feifei Luo Jun Zhang Wulian Chen Chen Jiang Jie Liu Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel
description	Abstract Paclitaxel (PTX), especially albumin-bound PTX in clinical, has displayed significant inhibition of tumor growth in patients. But the systemic distribution and poor water solubility of PTX often lead to severe side effects, consequently limiting the anti-tumor efficacy. In this study, we developed a novel PTX-loaded polymeric micelle drug delivery system. These self-assembled polymeric micelles from core to outside consisted of poly L-phenylalanine (pPhe), DTSSP linked poly L-lysine (pLys), poly ethylene glycol (PEG) and dehydroascorbic acids (DHA). pPhe formed the hydrophobic core to encapsulate PTX; DTSSPs on pLys covalently cross-linked and formed disulfide bond to stabilize PTX from loss in blood circulation; PEG improved solubility to lower toxicity of PTX for its high hydrophilicity; DHA targeted tumors by specifically recognizing GLUT1 mainly expressed on tumor cells. Thus, PTX would be precisely released into tumor cells with high dose of glutathione to break disulfide bond. Moreover, these PTX-loaded polymer micelles significantly suppressed tumor cell viability, proliferation, and migration in vitro, and also greatly inhibited tumor growth and prolonged survival in tumor-bearing mice without detectable side effects. Therefore, the new drug delivery system could reduce severe side effects and enhance anti-tumor efficacy of PTX via peripheral stabilization, low toxicity and tumor targeting.
format	article
author	Xiaoyu Pei Feifei Luo Jun Zhang Wulian Chen Chen Jiang Jie Liu
author_facet	Xiaoyu Pei Feifei Luo Jun Zhang Wulian Chen Chen Jiang Jie Liu
author_sort	Xiaoyu Pei
title	Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel
title_short	Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel
title_full	Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel
title_fullStr	Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel
title_full_unstemmed	Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel
title_sort	dehydroascorbic acids-modified polymer micelles target cancer cells to enhance anti-tumor efficacy of paclitaxel
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/de33b223e6dd412ebdab1df4a675e07f
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Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel

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