TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting

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ID: 19926
2014
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Abstract
Feng-Ying Chen,1 Jing-Jing Yan,1 Han-Xi Yi,2 Fu-Qiang Hu,2 Yong-Zhong Du,2 Hong Yuan,2 Jian You,2 Meng-Dan Zhao1 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2College of Pharmaceutical Science, Zhejiang University, Hangzhou, People’s Republic of China Abstract: Nowadays, a real challenge in cancer therapy is to design drug delivery systems that can achieve high concentrations of drugs at the target site for improved therapeutic effect with reduced side effects. In this research, we designed and synthesized a homing peptide-(TNYLFSPNGPIA, TNYL) modified chitosan-g-stearate (CS) polymer micelle (named T-CS) for targeting delivery. The peptide displayed specific binding affinity to EphB4 which is a member of the Eph family of receptor tyrosine protein kinases. The amphiphilic polymer T-CS can gather into micelles by themselves in an aqueous environment with a low critical micelle concentration value (91.2 µg/L) and nano-scaled size (82.1±2.8 nm). The drug encapsulation efficiency reached 86.43% after loading the hydrophobic drug doxorubicin (DOX). The cytotoxicity of T-CS/DOX against SKOV3 cells was enhanced by approximately 2.3-fold when compared with CS/DOX. The quantitative and qualitative analysis for cellular uptake indicated that TNYL modification can markedly increase cellular internalization in the EphB4-overexpressing SKOV3 cell line, especially with a short incubation time. It is interesting that relatively higher uptake of the T-CS/DOX micelles by SKOV3 cells (positive-EphB4) than A549 cells (negative-EphB4) was observed when the two cells were co-incubated. Furthermore, in vivo distribution experiment using a bilateral-tumor model showed that there was more fluorescence accumulation in the SKOV3 tumor than in the A549 tumor over the whole experiment. These results suggest that TNYL-modified CS micelles may be promising drug carriers as targeting therapy for the EphB4-overexpressing tumor. Keywords: chitosan-g-stearate, polymeric micelles, TNYL, active targeting, antitumor activity
Reference Key
fy2014tnylinternational Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors FY, Chen;JJ, Yan;HX, Yi;FQ, Hu;YZ, Du;H, Yuan;J, You;MD, Zhao;
Journal international journal of nanomedicine
Year 2014
DOI
DOI not found
URL
http://www.dovepress.com/tnyl-peptide-functional-chitosan-g-stearate-conjugate-micelles-for-tum-peer-reviewed-article-IJN
Keywords Keywords not found

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