Deshayes Sébastien, Morris May, Heitz Frédéric, Divita Gilles
Centre de Recherches de Biochimie Macromoléculaire, CRBM-CNRS, UMR5237, Department of Molecular Biophysics and Therapeutics, 1919 Route de Mende, 34293 Montpellier, France.
Adv Drug Deliv Rev. 2008 Mar 1;60(4-5):537-47. doi: 10.1016/j.addr.2007.09.005. Epub 2007 Oct 25.
The recent discovery of new potent therapeutic molecules which do not reach the clinic due to poor delivery and low bioavailability have made of delivery a key stone in therapeutic development. Several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs), which have been successfully applied for in vivo delivery of biomolecules and constitute very promising tools. Distinct families of CPPs have been described; some require chemical linkage between the drug and the carrier for cellular drug internalization while others like Pep-and MPG-families, form stable complexes with drugs depending on their chemical nature. Pep and MPG are short amphipathic peptides, which form stable nanoparticles with proteins and nucleic acids respectively. MPG and Pep based nanoparticles enter cells independently of the endosomal pathway and efficiently deliver cargoes in a fully biologically active form into a large variety of cell lines as well as in animal models. This review will focus on the mechanisms of non-covalent MPG and Pep-1 strategies and their applications in cultured cells and animal models.
近期发现了一些新的强效治疗性分子，但由于递送效果不佳和生物利用度低而未能进入临床应用，这使得递送成为治疗研发的关键环节。人们设计了多种技术来提高治疗性分子的细胞摄取，包括细胞穿透肽（CPPs），其已成功应用于生物分子的体内递送，是非常有前景的工具。已经描述了不同的CPPs家族；一些需要药物与载体之间进行化学连接以实现细胞内药物内化，而其他如Pep和MPG家族，则根据药物的化学性质与药物形成稳定的复合物。Pep和MPG是短的两亲性肽，分别与蛋白质和核酸形成稳定的纳米颗粒。基于MPG和Pep的纳米颗粒独立于内体途径进入细胞，并以完全生物活性的形式将货物有效递送至多种细胞系以及动物模型中。本综述将重点关注非共价MPG和Pep-1策略的机制及其在培养细胞和动物模型中的应用。
