Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China.
Institut de Chimie Pharmaceutique Albert Lespagnol (Lille 2) (ICPAL), 3 rue du Professeur Laguesse 59006, France.
Biomolecules. 2012 Mar 30;2(2):187-202. doi: 10.3390/biom2020187.
The cell membrane is a highly selective barrier. This limits the cellular uptake of molecules including DNA, oligonucleotides, peptides and proteins used as therapeutic agents. Different approaches have been employed to increase the membrane permeability and intracellular delivery of these therapeutic molecules. One such approach is the use of Cell Penetrating Peptides (CPPs). CPPs represent a new and innovative concept, which bypasses the problem of bioavailability of drugs. The success of CPPs lies in their ability to unlock intracellular and even intranuclear targets for the delivery of agents ranging from peptides to antibodies and drug-loaded nanoparticles. This review highlights the development of cell penetrating peptides for cell-specific delivery strategies involving biomolecules that can be triggered spatially and temporally within a cell transport pathway by change in physiological conditions. The review also discusses conjugations of therapeutic agents to CPPs for enhanced intracellular delivery and bioavailability that are at the clinical stage of development.
细胞膜是一种高度选择性的屏障。这限制了包括 DNA、寡核苷酸、肽和蛋白质在内的分子被细胞摄取，这些分子被用作治疗剂。已经采用了不同的方法来增加这些治疗分子的膜通透性和细胞内递呈。其中一种方法是使用细胞穿透肽（CPP）。CPP 代表了一种新的创新概念，它绕过了药物生物利用度的问题。CPP 的成功在于它们能够为从肽到抗体和载药纳米颗粒的各种药物解锁细胞内甚至核内靶标。本文综述了细胞穿透肽在涉及生物分子的细胞特异性递药策略中的发展，这些生物分子可以通过细胞内运输途径中生理条件的变化在空间和时间上被触发。本文还讨论了将治疗剂与 CPP 缀合以增强细胞内递呈和生物利用度的方法，这些方法正处于临床开发阶段。
