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

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ID: 183875
2011
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Abstract
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's Hospital, School of Medicine, Zhejiang University, Hangzhou, People'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 "angiogenesis." Some tumor cells within solid tumors can overexpress integrins αvβ3 and αvβ5, 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'-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 (αvβ3 and αvβ5) 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
Reference Key
ll2011internationalrgd Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Cai LL;Liu P;Li X;Huang X;Ye YQ;Chen FY;Yuan H;Hu FQ;Du YZ
Journal nonlinear analysis: real world applications
Year 2011
DOI
DOI not found
URL
http://www.dovepress.com/rgd-peptide-mediated-chitosan-based-polymeric-micelles-targeting-deliv-a8933
Keywords
Medicine (General)

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