School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Curr Pharm Des. 2018;24(5):541-548. doi: 10.2174/1381612823666170728094922.
Cell Penetrating Peptides (CPPs) equipped with a high penetrating ability are used as a promising tool to gain access to the cell interior, cross the cell membrane and deliver bioactive small or macromolecular cargos into the cytoplasm or nucleus. The superiority of wide range of applications, high transport efficiency and low biological toxicity make them particularly desirable in laboratory or clinical studies. Previous studies have shown that their non-selectivity and reaction with proteins in plasma hamper their application for tumor therapy, which might adversely affect the treatment effect and even induce some side effects. However, several recent studies have found that various kinds of modifiers of CPPs can effectively increase the target selectivity, reduce cytotoxicity to normal cells and produce multiple antitumor functions due to the different cleavable bonds which are sensitive to the tumor microenvironment or other novel designs. Apparently, these designs of 'smart' CPPs appear to be promising in the field of antitumor drug delivery. Here, we review these current improved approaches which mainly involve strategies of physical, chemical as well as biological pathways and we also explain the possible uptake mechanisms of direct penetration, internalization and escape which have been discussed in some publications with specific attention. In addition, some possible problems needed to be considered in the process of improving CPPs are discussed at the end of this review. This study aims to present an overview of the latest progress of CPPs, and provides a comprehensive theoretical background and reference guidance for future laboratory research and clinical application.
细胞穿透肽（CPPs）具有很强的穿透能力，被用作一种有前途的工具，能够进入细胞内部，穿过细胞膜，并将生物活性的小分子或生物大分子货物递送到细胞质或细胞核中。其广泛的应用范围、高效的传输效率和低生物毒性等优势，使它们在实验室或临床研究中特别受欢迎。以前的研究表明，它们的非选择性和与血浆中的蛋白质的反应，妨碍了它们在肿瘤治疗中的应用，这可能会对治疗效果产生不利影响，甚至会引发一些副作用。然而，最近的几项研究发现，各种 CPPs 的修饰剂可以有效地提高靶选择性，降低对正常细胞的细胞毒性，并由于不同的可切割键对肿瘤微环境或其他新设计的敏感性而产生多种抗肿瘤功能。显然，这些“智能”CPPs 的设计在抗肿瘤药物输送领域具有很大的应用前景。在这里，我们综述了这些当前改进的方法，主要涉及物理、化学以及生物途径的策略，我们还解释了一些出版物中讨论的直接穿透、内化和逃逸的可能摄取机制，并特别关注了这些机制。此外，在改进 CPPs 的过程中还需要考虑一些可能出现的问题，这在本文的结尾部分进行了讨论。本研究旨在对 CPPs 的最新进展进行综述，为未来的实验室研究和临床应用提供全面的理论背景和参考指导。
