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Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5
Cancer is the leading cause of death worldwide, and metastasis is the main attribute to cancer death. CXCR4 and its natural ligand CXCL12 have been known to play a critical role in tumorigenesis, angiogenesis and metastasis. Therefore, designing a new CXCR4 antagonist to prevent tumor metastasis wil...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549986/ https://www.ncbi.nlm.nih.gov/pubmed/28793338 http://dx.doi.org/10.1371/journal.pone.0182697 |
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author | Fang, Xiaocui Xie, Hanyi Duan, Hongyang Li, Ping Yousaf, Maryam Xu, Haiyan Yang, Yanlian Wang, Chen |
author_facet | Fang, Xiaocui Xie, Hanyi Duan, Hongyang Li, Ping Yousaf, Maryam Xu, Haiyan Yang, Yanlian Wang, Chen |
author_sort | Fang, Xiaocui |
collection | PubMed |
description | Cancer is the leading cause of death worldwide, and metastasis is the main attribute to cancer death. CXCR4 and its natural ligand CXCL12 have been known to play a critical role in tumorigenesis, angiogenesis and metastasis. Therefore, designing a new CXCR4 antagonist to prevent tumor metastasis will be of great significance. Herein, a novel chemically synthesized peptide (E5) that has an ability to target CXCR4/CXCL12 axis was loaded in micelle glycol-phosphatidylethanolamine (PEG-PE) block copolymer to form micelle-encapsulated E5 (M-E5). We demonstrated that M-E5 exhibited higher affinity for CXCR4-overexpressing MCF-7 and HepG2 tumor cells as compared to free E5, and efficiently inhibited the tumor cells migration. Mechanistic studies implied that PEG-PE micelle can encapsulate E5 and improve E5 targeting efficiency for CXCR4 by accumulating E5 on the tumor cell membrane. Furthermore, through encapsulation of chemotherapeutic drug doxorubicin (Dox) in PEG-PE micelle, we proved that PEG-PE micelle could serve as a co-carrier for both E5 and Dox (M-E5-Dox). M-E5 enhanced the efficiency of Dox by down-regulating the phosphorylation level of Akt, Erk and p38/MAPK proteins. In conclusion, PEG-PE micelle demonstrated a promising delivery system for E5, and M-E5 is expected to be a potential therapeutic agent that will help to improve the clinical benefits in current therapies used for solid tumors. |
format | Online Article Text |
id | pubmed-5549986 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55499862017-08-15 Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5 Fang, Xiaocui Xie, Hanyi Duan, Hongyang Li, Ping Yousaf, Maryam Xu, Haiyan Yang, Yanlian Wang, Chen PLoS One Research Article Cancer is the leading cause of death worldwide, and metastasis is the main attribute to cancer death. CXCR4 and its natural ligand CXCL12 have been known to play a critical role in tumorigenesis, angiogenesis and metastasis. Therefore, designing a new CXCR4 antagonist to prevent tumor metastasis will be of great significance. Herein, a novel chemically synthesized peptide (E5) that has an ability to target CXCR4/CXCL12 axis was loaded in micelle glycol-phosphatidylethanolamine (PEG-PE) block copolymer to form micelle-encapsulated E5 (M-E5). We demonstrated that M-E5 exhibited higher affinity for CXCR4-overexpressing MCF-7 and HepG2 tumor cells as compared to free E5, and efficiently inhibited the tumor cells migration. Mechanistic studies implied that PEG-PE micelle can encapsulate E5 and improve E5 targeting efficiency for CXCR4 by accumulating E5 on the tumor cell membrane. Furthermore, through encapsulation of chemotherapeutic drug doxorubicin (Dox) in PEG-PE micelle, we proved that PEG-PE micelle could serve as a co-carrier for both E5 and Dox (M-E5-Dox). M-E5 enhanced the efficiency of Dox by down-regulating the phosphorylation level of Akt, Erk and p38/MAPK proteins. In conclusion, PEG-PE micelle demonstrated a promising delivery system for E5, and M-E5 is expected to be a potential therapeutic agent that will help to improve the clinical benefits in current therapies used for solid tumors. Public Library of Science 2017-08-09 /pmc/articles/PMC5549986/ /pubmed/28793338 http://dx.doi.org/10.1371/journal.pone.0182697 Text en © 2017 Fang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Fang, Xiaocui Xie, Hanyi Duan, Hongyang Li, Ping Yousaf, Maryam Xu, Haiyan Yang, Yanlian Wang, Chen Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5 |
title | Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5 |
title_full | Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5 |
title_fullStr | Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5 |
title_full_unstemmed | Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5 |
title_short | Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5 |
title_sort | anti-tumor activity of nanomicelles encapsulating cxcr4 peptide antagonist e5 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549986/ https://www.ncbi.nlm.nih.gov/pubmed/28793338 http://dx.doi.org/10.1371/journal.pone.0182697 |
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