Patel Leena N, Zaro Jennica L, Shen Wei-Chiang
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA.
Pharm Res. 2007 Nov;24(11):1977-92. doi: 10.1007/s11095-007-9303-7. Epub 2007 Apr 19.
Cell penetrating peptides, generally categorized as amphipathic or cationic depending on their sequence, are increasingly drawing attention as a non-invasive delivery technology for macromolecules. Delivery of a diverse set of cargo in terms of size and nature ranging from small molecules to particulate cargo has been attempted using different types of cell penetrating peptides (CPPs) in vitro and in vivo. However, the internalization mechanism of CPPs is an unresolved issue to date, with dramatic changes in view regarding the involvement of endocytosis as a pathway of internalization. A key reason for the lack of consensus on the mechanism can be attributed to the methodology in deciphering the internalization mechanism. In this review, we highlight some of the methodology concerns, focus more on the internalization pathway and also provide a novel perspective about the intracellular processing of CPPs, which is a crucial aspect to consider when selecting a cell penetrating peptide as a drug delivery system. In addition, recent applications of cell penetrating peptides for the delivery of small molecules, peptides, proteins, oligonucleotides, nanoparticles and liposomes have been reviewed.
细胞穿透肽根据其序列一般可分为两亲性或阳离子性，作为一种用于大分子的非侵入性递送技术，正越来越受到关注。在体外和体内，人们尝试使用不同类型的细胞穿透肽（CPP）来递送从小分子到颗粒物质等各种大小和性质各异的货物。然而，CPP的内化机制至今仍是一个未解决的问题，关于内吞作用作为一种内化途径的参与情况，观点发生了巨大变化。在该机制上缺乏共识的一个关键原因可归因于解读内化机制的方法。在这篇综述中，我们强调了一些方法学问题，更多地关注内化途径，并提供了关于CPP细胞内加工的新观点，这是选择细胞穿透肽作为药物递送系统时需要考虑的一个关键方面。此外，还综述了细胞穿透肽最近在小分子、肽、蛋白质、寡核苷酸、纳米颗粒和脂质体递送方面的应用。
