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包裹CXCR4肽拮抗剂E5的纳米胶束的抗肿瘤活性

Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5.

作者信息

Fang Xiaocui, Xie Hanyi, Duan Hongyang, Li Ping, Yousaf Maryam, Xu Haiyan, Yang Yanlian, Wang Chen

机构信息

CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, P. R. China.

CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, P. R. China.

出版信息

PLoS One. 2017 Aug 9;12(8):e0182697. doi: 10.1371/journal.pone.0182697. eCollection 2017.

DOI:10.1371/journal.pone.0182697
PMID:28793338
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5549986/
Abstract

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.

摘要

癌症是全球主要死因，而转移是癌症致死的主要原因。已知CXCR4及其天然配体CXCL12在肿瘤发生、血管生成和转移中起关键作用。因此，设计一种新型CXCR4拮抗剂以预防肿瘤转移具有重要意义。在此，一种具有靶向CXCR4/CXCL12轴能力的新型化学合成肽（E5）被装载到胶束状乙二醇磷脂酰乙醇胺（PEG-PE）嵌段共聚物中，形成胶束包裹的E5（M-E5）。我们证明，与游离E5相比，M-E5对过表达CXCR4的MCF-7和HepG2肿瘤细胞表现出更高的亲和力，并有效抑制肿瘤细胞迁移。机制研究表明，PEG-PE胶束可以包裹E5，并通过将E5聚集在肿瘤细胞膜上提高其对CXCR4的靶向效率。此外，通过将化疗药物阿霉素（Dox）包裹在PEG-PE胶束中，我们证明PEG-PE胶束可以作为E5和Dox的共载体（M-E5-Dox）。M-E5通过下调Akt、Erk和p38/MAPK蛋白的磷酸化水平提高了Dox的疗效。总之，PEG-PE胶束是一种有前景的E5递送系统，M-E5有望成为一种潜在的治疗剂，有助于改善目前用于实体瘤治疗的临床疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca53/5549986/14e309444f5b/pone.0182697.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca53/5549986/833470ac9a08/pone.0182697.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca53/5549986/ca4510d85a46/pone.0182697.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca53/5549986/2236e866ad17/pone.0182697.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca53/5549986/14e309444f5b/pone.0182697.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca53/5549986/833470ac9a08/pone.0182697.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca53/5549986/dca9de44bd5a/pone.0182697.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca53/5549986/24fd13e5afde/pone.0182697.g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca53/5549986/14e309444f5b/pone.0182697.g008.jpg

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