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病毒及其他细胞穿透肽作为医学中治疗药物的载体

Viral and other cell-penetrating peptides as vectors of therapeutic agents in medicine.

作者信息

Durzyńska Julia, Przysiecka Łucja, Nawrot Robert, Barylski Jakub, Nowicki Grzegorz, Warowicka Alicja, Musidlak Oskar, Goździcka-Józefiak Anna

机构信息

Department of Molecular Virology (J.D., R.N., J.B., G.N., O.M., A.G.-J.), and NanoBioMedical Center (Ł.P., A.W.), Adam Mickiewicz University, Poznań, Poland

Department of Molecular Virology (J.D., R.N., J.B., G.N., O.M., A.G.-J.), and NanoBioMedical Center (Ł.P., A.W.), Adam Mickiewicz University, Poznań, Poland.

出版信息

J Pharmacol Exp Ther. 2015 Jul;354(1):32-42. doi: 10.1124/jpet.115.223305. Epub 2015 Apr 28.

DOI:10.1124/jpet.115.223305
PMID:25922342
Abstract

Efficient delivery of heterologous molecules for treatment of cells is a great challenge in modern medicine and pharmacology. Cell-penetrating peptides (CPPs) may improve efficient delivery of a wide range of macromolecular cargos, including plasmid DNA, small interfering RNA, drugs, nanoparticulate pharmaceutical carriers, and anticancer drugs. In this paper, we present the history of CPPs' discovery with special attention drawn to sequences of viral origin. We also describe different CPP families with regard to their physicochemical properties and numerous mechanisms of CPP cell uptake by direct penetration and endocytotic pathways. A detailed description is focused on formation of carrier-cargo complexes, which are needed for practical use of CPPs in medicine and biotechnology. Examples of successful application of CPPs in treatment of human diseases are also presented, including decreased tumor growth and induction of cancer cell death. Finally, we review modern design approaches to novel CPPs and prediction of their activity. To sum up, the current review presents a thorough and up-to-date knowledge of CPPs and may be a valuable source of information for researchers in pharmacology designing new therapeutic agents.

摘要

在现代医学和药理学中,高效递送异源分子用于细胞治疗是一项巨大挑战。细胞穿透肽(CPPs)可改善多种大分子货物的高效递送,这些货物包括质粒DNA、小干扰RNA、药物、纳米颗粒药物载体和抗癌药物。在本文中,我们介绍了CPPs的发现历程,并特别关注了病毒来源的序列。我们还根据其物理化学性质以及通过直接穿透和内吞途径摄取CPPs的众多机制,描述了不同的CPP家族。详细描述聚焦于载体-货物复合物的形成,这是CPPs在医学和生物技术中的实际应用所必需的。还介绍了CPPs在治疗人类疾病方面成功应用的实例,包括肿瘤生长的减缓以及癌细胞死亡的诱导。最后,我们综述了新型CPPs的现代设计方法及其活性预测。总之,本综述全面且最新地介绍了CPPs的知识,可能为药理学领域设计新治疗药物的研究人员提供有价值的信息来源。

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