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TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting
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 chi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186491/ https://www.ncbi.nlm.nih.gov/pubmed/25298734 http://dx.doi.org/10.2147/IJN.S69572 |
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author | Chen, Feng-Ying Yan, Jing-Jing Yi, Han-Xi Hu, Fu-Qiang Du, Yong-Zhong Yuan, Hong You, Jian Zhao, Meng-Dan |
author_facet | Chen, Feng-Ying Yan, Jing-Jing Yi, Han-Xi Hu, Fu-Qiang Du, Yong-Zhong Yuan, Hong You, Jian Zhao, Meng-Dan |
author_sort | Chen, Feng-Ying |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4186491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41864912014-10-08 TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting Chen, Feng-Ying Yan, Jing-Jing Yi, Han-Xi Hu, Fu-Qiang Du, Yong-Zhong Yuan, Hong You, Jian Zhao, Meng-Dan Int J Nanomedicine Original Research 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. Dove Medical Press 2014-09-26 /pmc/articles/PMC4186491/ /pubmed/25298734 http://dx.doi.org/10.2147/IJN.S69572 Text en © 2014 Chen et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Chen, Feng-Ying Yan, Jing-Jing Yi, Han-Xi Hu, Fu-Qiang Du, Yong-Zhong Yuan, Hong You, Jian Zhao, Meng-Dan TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting |
title | TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting |
title_full | TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting |
title_fullStr | TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting |
title_full_unstemmed | TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting |
title_short | TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting |
title_sort | tnyl peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186491/ https://www.ncbi.nlm.nih.gov/pubmed/25298734 http://dx.doi.org/10.2147/IJN.S69572 |
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