Department of Pharmaceutical Sciences, College of Pharmacy, The University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109-1065.
J Biomed Mater Res A. 2014 Feb;102(2):575-87. doi: 10.1002/jbm.a.34859. Epub 2013 Jul 30.
One of the major hurdles to cure cancer lies in the low potency of currently available drugs, which could eventually be solved by using more potent therapeutic macromolecules, such as proteins or genes. However, although these macromolecules possess greater potency inside the cancer cells, the barely permeable cell membrane remains a formidable barrier to exert their efficacy. A widely used strategy is to use cell penetrating peptides (CPPs) to improve their intracellular uptake. Since the discovery of the first CPP, numerous CPPs have been derived from natural or synthesized products. Both in vitro and in vivo studies have demonstrated that those CPPs are highly efficient in transducing cargoes into almost all cell types. Therefore, to date, CPPs have been widely used for intracellular delivery of various cargoes, including peptides, proteins, genes, and even nanoparticles. In addition, recently, based on the successes of CPPs in cellular studies, their applications in vivo have been actively pursued. This review will focus on the advanced applications of CPP-based in vivo delivery of therapeutics (e.g., small molecule drugs, proteins, and genes). In addition, we will highlight certain updated applications of CPPs for intracellular delivery of nanoparticulate drug carriers, as well as several "smart" strategies for tumor targeted delivery of CPP-cargoes.
癌症治疗的主要障碍之一在于现有药物的效力较低，这最终可以通过使用更有效的治疗性大分子（如蛋白质或基因）来解决。然而，尽管这些大分子在癌细胞内具有更大的效力，但几乎不可渗透的细胞膜仍然是发挥其疗效的一个巨大障碍。一种广泛使用的策略是使用细胞穿透肽（CPPs）来提高它们的细胞内摄取。自第一个 CPP 被发现以来，已经从天然或合成产品中衍生出了许多 CPP。体外和体内研究都表明，这些 CPP 能够高效地将 cargo 转导到几乎所有类型的细胞中。因此，迄今为止，CPP 已被广泛用于各种 cargo 的细胞内递送，包括肽、蛋白质、基因，甚至纳米颗粒。此外，最近，基于 CPP 在细胞研究中的成功，它们在体内的应用也在积极探索中。这篇综述将重点介绍基于 CPP 的治疗剂体内递药的最新应用（例如小分子药物、蛋白质和基因）。此外，我们还将重点介绍 CPP 用于细胞内递送纳米药物载体的一些最新应用，以及 CPP-cargo 肿瘤靶向递药的几种“智能”策略。
