Self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis

Traditional chemotherapy exhibits a certain therapeutic effect toward malignant cancer, but easily induce tumor multidrug resistance (MDR), thereby resulting in the progress of tumor recurrence or metastasis. In this work, we deigned ternary hybrid nanodrugs (PEI/DOX@CXB-NPs) to simultaneously comba...

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Autores principales:	Xu Cheng, Dapeng Li, Jiaxi Xu, Bing Wei, Qin Fang, Longshun Yang, Yanbing Xue, Xin Wang, Rupei Tang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Drugs dimer Multidrug resistance Metastasis Charge reversal Proton sponge Redox sensitive Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d5df5efdbff347129415b5f6fb84d986
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spelling	oai:doaj.org-article:d5df5efdbff347129415b5f6fb84d9862021-12-02T05:01:22ZSelf-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis2211-383510.1016/j.apsb.2021.03.041https://doaj.org/article/d5df5efdbff347129415b5f6fb84d9862021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211383521001131https://doaj.org/toc/2211-3835Traditional chemotherapy exhibits a certain therapeutic effect toward malignant cancer, but easily induce tumor multidrug resistance (MDR), thereby resulting in the progress of tumor recurrence or metastasis. In this work, we deigned ternary hybrid nanodrugs (PEI/DOX@CXB-NPs) to simultaneously combat against tumor MDR and metastasis. In vitro results demonstrate this hybrid nanodrugs could efficiently increase cellular uptake at pH 6.8 by the charge reversal, break lysosomal sequestration by the proton sponge effect and trigger drugs release by intracellular GSH, eventually leading to higher drugs accumulation and cell-killing in drug-sensitive/resistant cells. In vivo evaluation revealed that this nanodrugs could significantly inhibit MDR tumor growth and simultaneously prevent A549 tumor liver/lung metastasis owing to the specifically drugs accumulation. Mechanism studies further verified that hybrid nanodrugs were capable of down-regulating the expression of MDR or metastasis-associated proteins, lead to the enhanced anti-MDR and anti-metastasis effect. As a result, the multiple combination strategy provided an option for effective cancer treatment, which could be potentially extended to other therapeutic agents or further use in clinical test.Xu ChengDapeng LiJiaxi XuBing WeiQin FangLongshun YangYanbing XueXin WangRupei TangElsevierarticleDrugs dimerMultidrug resistanceMetastasisCharge reversalProton spongeRedox sensitiveTherapeutics. PharmacologyRM1-950ENActa Pharmaceutica Sinica B, Vol 11, Iss 11, Pp 3595-3607 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Drugs dimer Multidrug resistance Metastasis Charge reversal Proton sponge Redox sensitive Therapeutics. Pharmacology RM1-950
spellingShingle	Drugs dimer Multidrug resistance Metastasis Charge reversal Proton sponge Redox sensitive Therapeutics. Pharmacology RM1-950 Xu Cheng Dapeng Li Jiaxi Xu Bing Wei Qin Fang Longshun Yang Yanbing Xue Xin Wang Rupei Tang Self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis
description	Traditional chemotherapy exhibits a certain therapeutic effect toward malignant cancer, but easily induce tumor multidrug resistance (MDR), thereby resulting in the progress of tumor recurrence or metastasis. In this work, we deigned ternary hybrid nanodrugs (PEI/DOX@CXB-NPs) to simultaneously combat against tumor MDR and metastasis. In vitro results demonstrate this hybrid nanodrugs could efficiently increase cellular uptake at pH 6.8 by the charge reversal, break lysosomal sequestration by the proton sponge effect and trigger drugs release by intracellular GSH, eventually leading to higher drugs accumulation and cell-killing in drug-sensitive/resistant cells. In vivo evaluation revealed that this nanodrugs could significantly inhibit MDR tumor growth and simultaneously prevent A549 tumor liver/lung metastasis owing to the specifically drugs accumulation. Mechanism studies further verified that hybrid nanodrugs were capable of down-regulating the expression of MDR or metastasis-associated proteins, lead to the enhanced anti-MDR and anti-metastasis effect. As a result, the multiple combination strategy provided an option for effective cancer treatment, which could be potentially extended to other therapeutic agents or further use in clinical test.
format	article
author	Xu Cheng Dapeng Li Jiaxi Xu Bing Wei Qin Fang Longshun Yang Yanbing Xue Xin Wang Rupei Tang
author_facet	Xu Cheng Dapeng Li Jiaxi Xu Bing Wei Qin Fang Longshun Yang Yanbing Xue Xin Wang Rupei Tang
author_sort	Xu Cheng
title	Self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis
title_short	Self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis
title_full	Self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis
title_fullStr	Self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis
title_full_unstemmed	Self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis
title_sort	self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/d5df5efdbff347129415b5f6fb84d986
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Self-assembled ternary hybrid nanodrugs for overcoming tumor resistance and metastasis

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