pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Qiang Huo,1,* Jianhua Zhu,1,2,* Yimin Niu,3 Huihui Shi,2 Yaxiang Gong,2 Yang Li,2 Huihui Song,4 Yang Liu2 1School of Pharmacy, Bengbu Medical College, Bengbu, 2School of Pharmacy, Nanjing Medical University, 3Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjin...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Huo Q, Zhu J, Niu Y, Shi H, Gong Y, Li Y, Song H, Liu Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	pH-response Charge reversal Multidrug resistance Paclitaxel Disulfiram Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/47207e0997344edc847a55c112624051
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:47207e0997344edc847a55c112624051
record_format	dspace
spelling	oai:doaj.org-article:47207e0997344edc847a55c1126240512021-12-02T01:45:09ZpH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer1178-2013https://doaj.org/article/47207e0997344edc847a55c1126240512017-12-01T00:00:00Zhttps://www.dovepress.com/ph-triggered-surface-charge-switchable-polymer-micelles-for-the-co-del-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Qiang Huo,1,* Jianhua Zhu,1,2,* Yimin Niu,3 Huihui Shi,2 Yaxiang Gong,2 Yang Li,2 Huihui Song,4 Yang Liu2 1School of Pharmacy, Bengbu Medical College, Bengbu, 2School of Pharmacy, Nanjing Medical University, 3Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 4Yangtze River Pharmaceutical Group, Taizhou, People’s Republic of China *These authors contributed equally to this work Abstract: Multidrug resistance (MDR) remains a major challenge for providing effective chemotherapy for many cancer patients. To address this issue, we report an intelligent polymer-based drug co-delivery system which could enhance and accelerate cellular uptake and reverse MDR. The nanodrug delivery systems were constructed by encapsulating disulfiram (DSF), a P-glycoprotein (P-gp) inhibitor, into the hydrophobic core of poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLL) block copolymer micelles, as well as 2,3-dimethylmaleic anhydride (DMA) and paclitaxel (PTX) were grafted on the side chain of l-lysine simultaneously. The surface charge of the drug-loaded micelles represents as negative in plasma (pH 7.4), which is helpful to prolong the circulation time, and in a weak acid environment of tumor tissue (pH 6.5–6.8) it can be reversed to positive, which is in favor of their entering into the cancer cells. In addition, the carrier could release DSF and PTX successively inside cells. The results of in vitro studies show that, compared to the control group, the DSF and PTX co-loaded micelles with charge reversal exhibits more effective cellular uptake and significantly increased cytotoxicity of PTX to MCF-7/ADR cells which may be due to the inhibitory effect of DSF on the efflux function of P-gp. Accordingly, such a smart pH-sensitive nanosystem, in our opinion, possesses significant potential to achieve combinational drug delivery and overcome drug resistance in cancer therapy. Keywords: pH response, charge reversal, multidrug resistance, paclitaxel, disulfiramHuo QZhu JNiu YShi HGong YLi YSong HLiu YDove Medical PressarticlepH-responseCharge reversalMultidrug resistancePaclitaxelDisulfiramMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8631-8647 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	pH-response Charge reversal Multidrug resistance Paclitaxel Disulfiram Medicine (General) R5-920
spellingShingle	pH-response Charge reversal Multidrug resistance Paclitaxel Disulfiram Medicine (General) R5-920 Huo Q Zhu J Niu Y Shi H Gong Y Li Y Song H Liu Y pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer
description	Qiang Huo,1,* Jianhua Zhu,1,2,* Yimin Niu,3 Huihui Shi,2 Yaxiang Gong,2 Yang Li,2 Huihui Song,4 Yang Liu2 1School of Pharmacy, Bengbu Medical College, Bengbu, 2School of Pharmacy, Nanjing Medical University, 3Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 4Yangtze River Pharmaceutical Group, Taizhou, People’s Republic of China *These authors contributed equally to this work Abstract: Multidrug resistance (MDR) remains a major challenge for providing effective chemotherapy for many cancer patients. To address this issue, we report an intelligent polymer-based drug co-delivery system which could enhance and accelerate cellular uptake and reverse MDR. The nanodrug delivery systems were constructed by encapsulating disulfiram (DSF), a P-glycoprotein (P-gp) inhibitor, into the hydrophobic core of poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLL) block copolymer micelles, as well as 2,3-dimethylmaleic anhydride (DMA) and paclitaxel (PTX) were grafted on the side chain of l-lysine simultaneously. The surface charge of the drug-loaded micelles represents as negative in plasma (pH 7.4), which is helpful to prolong the circulation time, and in a weak acid environment of tumor tissue (pH 6.5–6.8) it can be reversed to positive, which is in favor of their entering into the cancer cells. In addition, the carrier could release DSF and PTX successively inside cells. The results of in vitro studies show that, compared to the control group, the DSF and PTX co-loaded micelles with charge reversal exhibits more effective cellular uptake and significantly increased cytotoxicity of PTX to MCF-7/ADR cells which may be due to the inhibitory effect of DSF on the efflux function of P-gp. Accordingly, such a smart pH-sensitive nanosystem, in our opinion, possesses significant potential to achieve combinational drug delivery and overcome drug resistance in cancer therapy. Keywords: pH response, charge reversal, multidrug resistance, paclitaxel, disulfiram
format	article
author	Huo Q Zhu J Niu Y Shi H Gong Y Li Y Song H Liu Y
author_facet	Huo Q Zhu J Niu Y Shi H Gong Y Li Y Song H Liu Y
author_sort	Huo Q
title	pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer
title_short	pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer
title_full	pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer
title_fullStr	pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer
title_full_unstemmed	pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer
title_sort	ph-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/47207e0997344edc847a55c112624051
work_keys_str_mv	AT huoq phtriggeredsurfacechargeswitchablepolymermicellesforthecodeliveryofpaclitaxeldisulfiramandovercomingmultidrugresistanceincancer AT zhuj phtriggeredsurfacechargeswitchablepolymermicellesforthecodeliveryofpaclitaxeldisulfiramandovercomingmultidrugresistanceincancer AT niuy phtriggeredsurfacechargeswitchablepolymermicellesforthecodeliveryofpaclitaxeldisulfiramandovercomingmultidrugresistanceincancer AT shih phtriggeredsurfacechargeswitchablepolymermicellesforthecodeliveryofpaclitaxeldisulfiramandovercomingmultidrugresistanceincancer AT gongy phtriggeredsurfacechargeswitchablepolymermicellesforthecodeliveryofpaclitaxeldisulfiramandovercomingmultidrugresistanceincancer AT liy phtriggeredsurfacechargeswitchablepolymermicellesforthecodeliveryofpaclitaxeldisulfiramandovercomingmultidrugresistanceincancer AT songh phtriggeredsurfacechargeswitchablepolymermicellesforthecodeliveryofpaclitaxeldisulfiramandovercomingmultidrugresistanceincancer AT liuy phtriggeredsurfacechargeswitchablepolymermicellesforthecodeliveryofpaclitaxeldisulfiramandovercomingmultidrugresistanceincancer
_version_	1718402892537266176

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Ejemplares similares