RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells

Li-Li Cai1, Ping Liu1, Xi Li1, Xuan Huang2, Yi-Qing Ye3, Feng-Ying Chen3, Hong Yuan1, Fu-Qiang Hu1, Yong-Zhong Du11College of Pharmaceutical Science, Zhejiang University, Hangzhou, 2Department of Pharmacy, School of Medicine, Jiaxing College, Jiaxing, Zhejiang, 3Women&#39;s Hospital, School...

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Autores principales:	Cai LL, Liu P, Li X, Huang X, Ye YQ, Chen FY, Yuan H, Hu FQ, Du YZ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/989ccf3d334f4441b8abe6c8fa198000
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spelling	oai:doaj.org-article:989ccf3d334f4441b8abe6c8fa1980002021-12-02T01:30:29ZRGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells1176-91141178-2013https://doaj.org/article/989ccf3d334f4441b8abe6c8fa1980002011-12-01T00:00:00Zhttp://www.dovepress.com/rgd-peptide-mediated-chitosan-based-polymeric-micelles-targeting-deliv-a8933https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Li-Li Cai1, Ping Liu1, Xi Li1, Xuan Huang2, Yi-Qing Ye3, Feng-Ying Chen3, Hong Yuan1, Fu-Qiang Hu1, Yong-Zhong Du11College of Pharmaceutical Science, Zhejiang University, Hangzhou, 2Department of Pharmacy, School of Medicine, Jiaxing College, Jiaxing, Zhejiang, 3Women&#39;s Hospital, School of Medicine, Zhejiang University, Hangzhou, People&#39;s Republic of ChinaBackground: Solid tumors need new blood vessels to feed and nourish them as well as to allow tumor cells to escape into the circulation and lodge in other organs, which is termed &quot;angiogenesis.&quot; Some tumor cells within solid tumors can overexpress integrins &alpha;v&beta;3 and &alpha;v&beta;5, which can specifically recognize the peptide motif Arg-Gly-Asp (RGD). Thus, the targeting of RGD-modified micelles to tumor vasculature is a promising strategy for tumor-targeting treatment.Methods: RGD peptide (GSSSGRGDSPA) was coupled to poly(ethylene glycol)-modified stearic acid-grafted chitosan (PEG-CS-SA) micelles via chemical reaction in the presence of N,N&#39;-Disuccinimidyl carbonate. The critical micelle concentration of the polymeric micelles was determined by measuring the fluorescence intensity of pyrene as a fluorescent probe. The micelle size, size distribution, and zeta potential were measured by light scattering and electrophoretic mobility. Doxorubicin (DOX) was chosen as a model anticancer drug to investigate the drug entrapment efficiency, in vitro drug-release profile, and in vitro antitumor activities of drug-loaded RGD-PEG-CS-SA micelles in cells that overexpress integrins (&alpha;v&beta;3 and &alpha;v&beta;5) and integrin-deficient cells.Results: Using DOX as a model drug, the drug encapsulation efficiency could reach 90%, and the in vitro drug-release profiles suggested that the micelles could be used as a controlled-release carrier for the hydrophobic drug. Qualitative and quantitative analysis of cellular uptake indicated that RGD-modified micelles could significantly increase the DOX concentration in integrin-overexpressing human hepatocellular carcinoma cell line (BEL-7402), but not in human epithelial carcinoma cell line (Hela). The competitive cellular-uptake test showed that the cellular uptake of RGD-modified micelles in BEL-7402 cells was significantly inhibited in the presence of excess free RGD peptides. In vitro cytotoxicity tests demonstrated DOX-loaded RGD-modified micelles could specifically enhance the cytotoxicity against BEL-7402 compared with DOX-loaded PEG-CS-SA and doxorubicin hydrochlorate.Conclusion: This study suggests that RGD-modified PEG-CS-SA micelles are promising drug carriers for integrin-overexpressing tumor active targeting therapy.Keywords: cellular uptake, chitosan polymeric micelles, cytotoxicity, doxorubicin, integrin, RGD peptideCai LLLiu PLi XHuang XYe YQChen FYYuan HHu FQDu YZDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 3499-3508 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Cai LL Liu P Li X Huang X Ye YQ Chen FY Yuan H Hu FQ Du YZ RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells
description	Li-Li Cai1, Ping Liu1, Xi Li1, Xuan Huang2, Yi-Qing Ye3, Feng-Ying Chen3, Hong Yuan1, Fu-Qiang Hu1, Yong-Zhong Du11College of Pharmaceutical Science, Zhejiang University, Hangzhou, 2Department of Pharmacy, School of Medicine, Jiaxing College, Jiaxing, Zhejiang, 3Women&#39;s Hospital, School of Medicine, Zhejiang University, Hangzhou, People&#39;s Republic of ChinaBackground: Solid tumors need new blood vessels to feed and nourish them as well as to allow tumor cells to escape into the circulation and lodge in other organs, which is termed &quot;angiogenesis.&quot; Some tumor cells within solid tumors can overexpress integrins &alpha;v&beta;3 and &alpha;v&beta;5, which can specifically recognize the peptide motif Arg-Gly-Asp (RGD). Thus, the targeting of RGD-modified micelles to tumor vasculature is a promising strategy for tumor-targeting treatment.Methods: RGD peptide (GSSSGRGDSPA) was coupled to poly(ethylene glycol)-modified stearic acid-grafted chitosan (PEG-CS-SA) micelles via chemical reaction in the presence of N,N&#39;-Disuccinimidyl carbonate. The critical micelle concentration of the polymeric micelles was determined by measuring the fluorescence intensity of pyrene as a fluorescent probe. The micelle size, size distribution, and zeta potential were measured by light scattering and electrophoretic mobility. Doxorubicin (DOX) was chosen as a model anticancer drug to investigate the drug entrapment efficiency, in vitro drug-release profile, and in vitro antitumor activities of drug-loaded RGD-PEG-CS-SA micelles in cells that overexpress integrins (&alpha;v&beta;3 and &alpha;v&beta;5) and integrin-deficient cells.Results: Using DOX as a model drug, the drug encapsulation efficiency could reach 90%, and the in vitro drug-release profiles suggested that the micelles could be used as a controlled-release carrier for the hydrophobic drug. Qualitative and quantitative analysis of cellular uptake indicated that RGD-modified micelles could significantly increase the DOX concentration in integrin-overexpressing human hepatocellular carcinoma cell line (BEL-7402), but not in human epithelial carcinoma cell line (Hela). The competitive cellular-uptake test showed that the cellular uptake of RGD-modified micelles in BEL-7402 cells was significantly inhibited in the presence of excess free RGD peptides. In vitro cytotoxicity tests demonstrated DOX-loaded RGD-modified micelles could specifically enhance the cytotoxicity against BEL-7402 compared with DOX-loaded PEG-CS-SA and doxorubicin hydrochlorate.Conclusion: This study suggests that RGD-modified PEG-CS-SA micelles are promising drug carriers for integrin-overexpressing tumor active targeting therapy.Keywords: cellular uptake, chitosan polymeric micelles, cytotoxicity, doxorubicin, integrin, RGD peptide
format	article
author	Cai LL Liu P Li X Huang X Ye YQ Chen FY Yuan H Hu FQ Du YZ
author_facet	Cai LL Liu P Li X Huang X Ye YQ Chen FY Yuan H Hu FQ Du YZ
author_sort	Cai LL
title	RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells
title_short	RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells
title_full	RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells
title_fullStr	RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells
title_full_unstemmed	RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells
title_sort	rgd peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/989ccf3d334f4441b8abe6c8fa198000
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RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells

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