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细胞穿透肽基抗癌疗法的最新进展。

Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies.

机构信息

INSERM U976, Institut de Recherche St Louis, 1 avenue Claude Vellefaux, 75010 Paris, France.

Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France.

出版信息

Molecules. 2019 Mar 7;24(5):927. doi: 10.3390/molecules24050927.


DOI:10.3390/molecules24050927
PMID:30866424
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6429072/
Abstract

Cell-penetrating-peptides (CPPs) are small amino-acid sequences characterized by their ability to cross cellular membranes. They can transport various bioactive cargos inside cells including nucleic acids, large proteins, and other chemical compounds. Since 1988, natural and synthetic CPPs have been developed for applications ranging from fundamental to applied biology (cell imaging, gene editing, therapeutics delivery). In recent years, a great number of studies reported the potential of CPPs as carriers for the treatment of various diseases. Apart from a good efficacy due to a rapid and potent delivery, a crucial advantage of CPP-based therapies is the peptides low toxicity compared to most drug carriers. On the other hand, they are quite unstable and lack specificity. Higher specificity can be obtained using a cell-specific CPP to transport the therapeutic agent or using a non-specific CPP to transport a cargo with a targeted activity. CPP-cargo complexes can also be conjugated to another moiety that brings cell- or tissue-specificity. Studies based on all these approaches are showing promising results. Here, we focus on recent advances in the potential usage of CPPs in the context of cancer therapy, with a particular interest in CPP-mediated delivery of anti-tumoral proteins.

摘要

细胞穿透肽(CPPs)是一类具有穿过细胞膜能力的小氨基酸序列。它们可以将各种生物活性 cargo 输送到细胞内,包括核酸、大型蛋白质和其他化学化合物。自 1988 年以来,天然和合成的 CPP 已被开发用于从基础到应用生物学的各种应用(细胞成像、基因编辑、治疗剂递送)。近年来,大量研究报告了 CPP 作为治疗各种疾病的载体的潜力。除了由于快速和有效的递送而产生的良好疗效外,基于 CPP 的治疗的一个关键优势是与大多数药物载体相比,肽的毒性较低。另一方面,它们相当不稳定且缺乏特异性。使用细胞特异性 CPP 来输送治疗剂或使用具有靶向活性的非特异性 CPP 来输送货物可以获得更高的特异性。CPP-cargo 复合物也可以与另一种部分缀合,从而带来细胞或组织特异性。基于所有这些方法的研究正在显示出有希望的结果。在这里,我们专注于 CPP 在癌症治疗中的潜在用途的最新进展,特别关注 CPP 介导的抗肿瘤蛋白的递送来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43d9/6429072/da8a83355c22/molecules-24-00927-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43d9/6429072/f642f85ec480/molecules-24-00927-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43d9/6429072/da8a83355c22/molecules-24-00927-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43d9/6429072/f642f85ec480/molecules-24-00927-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43d9/6429072/da8a83355c22/molecules-24-00927-g002.jpg

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Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies.

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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Membrane Mechanics in Living Cells.

Dev Cell. 2019-1-7

[2]
Inhibition of Inflammatory Changes in Human Myometrial Cells by Cell Penetrating Peptide and Small Molecule Inhibitors of NFκB.

Front Immunol. 2018-12-20

[3]
New Cell-Penetrating Peptide (KRP) with Multiple Physicochemical Properties Endows Doxorubicin with Tumor Targeting and Improves Its Therapeutic Index.

ACS Appl Mater Interfaces. 2019-1-3

[4]
HIF-1α-derived cell-penetrating peptides inhibit ERK-dependent activation of HIF-1 and trigger apoptosis of cancer cells under hypoxia.

Cell Mol Life Sci. 2018-12-10

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J Cell Physiol. 2018-12-4

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Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore.

Proc Natl Acad Sci U S A. 2018-11-5

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Artif Cells Nanomed Biotechnol. 2018-10-12

[10]
Macropinocytosis activated by oncogenic Dbl enables specific targeted delivery of Tat/pDNA nano-complexes into ovarian cancer cells.

Int J Nanomedicine. 2018-8-30

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