Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells

Tuan Hiep Tran,1 Thiruganesh Ramasamy,1 Ju Yeon Choi,1 Hanh Thuy Nguyen,1 Thanh Tung Pham,1 Jee-Heon Jeong,1 Sae Kwang Ku,2 Han-Gon Choi,3 Chul Soon Yong,1 Jong Oh Kim11College of Pharmacy, Yeungnam University, Dae-Dong, 2College of Korean Medicine, Daegu Haany University, Gyeongsan, 3College of Pha...

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Autores principales:	Tran TH, Ramasamy T, Choi JY, Nguyen HT, Pham TT, Jeong JH, Ku SK, Choi HG, Yong CS, Kim JO
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/987a168acce5423c99ec071a8425d995
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spelling	oai:doaj.org-article:987a168acce5423c99ec071a8425d9952021-12-02T05:08:59ZTumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells1178-2013https://doaj.org/article/987a168acce5423c99ec071a8425d9952015-08-01T00:00:00Zhttp://www.dovepress.com/tumor-targeting-ph-sensitive-nanoparticles-for-docetaxel-delivery-to-d-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tuan Hiep Tran,1 Thiruganesh Ramasamy,1 Ju Yeon Choi,1 Hanh Thuy Nguyen,1 Thanh Tung Pham,1 Jee-Heon Jeong,1 Sae Kwang Ku,2 Han-Gon Choi,3 Chul Soon Yong,1 Jong Oh Kim11College of Pharmacy, Yeungnam University, Dae-Dong, 2College of Korean Medicine, Daegu Haany University, Gyeongsan, 3College of Pharmacy, Hanyang University, Hanyangdaehak-ro, Sangnok-gu, Ansan, South KoreaAbstract: The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.Keywords: docetaxel, polyaspartic acid, drug delivery systems, antitumor, pH-sensitiveTran THRamasamy TChoi JYNguyen HTPham TTJeong JHKu SKChoi HGYong CSKim JODove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5249-5262 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Tran TH Ramasamy T Choi JY Nguyen HT Pham TT Jeong JH Ku SK Choi HG Yong CS Kim JO Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells
description	Tuan Hiep Tran,1 Thiruganesh Ramasamy,1 Ju Yeon Choi,1 Hanh Thuy Nguyen,1 Thanh Tung Pham,1 Jee-Heon Jeong,1 Sae Kwang Ku,2 Han-Gon Choi,3 Chul Soon Yong,1 Jong Oh Kim11College of Pharmacy, Yeungnam University, Dae-Dong, 2College of Korean Medicine, Daegu Haany University, Gyeongsan, 3College of Pharmacy, Hanyang University, Hanyangdaehak-ro, Sangnok-gu, Ansan, South KoreaAbstract: The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.Keywords: docetaxel, polyaspartic acid, drug delivery systems, antitumor, pH-sensitive
format	article
author	Tran TH Ramasamy T Choi JY Nguyen HT Pham TT Jeong JH Ku SK Choi HG Yong CS Kim JO
author_facet	Tran TH Ramasamy T Choi JY Nguyen HT Pham TT Jeong JH Ku SK Choi HG Yong CS Kim JO
author_sort	Tran TH
title	Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells
title_short	Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells
title_full	Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells
title_fullStr	Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells
title_full_unstemmed	Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells
title_sort	tumor-targeting, ph-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/987a168acce5423c99ec071a8425d995
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Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells

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