Robert F. Smith School of Chemical and Biomolecular Engineering , Cornell University , 120 Olin Hall , Ithaca , New York 14853 , United States.
Bioconjug Chem. 2018 Aug 15;29(8):2628-2635. doi: 10.1021/acs.bioconjchem.8b00336. Epub 2018 Jul 10.
Intracellular drug delivery systems are often limited by their poor serum stability and delivery efficiency. Cell-penetrating peptides (CPPs), particularly those derived from basic protein subunits, have been studied extensively in this regard and used for the delivery of a variety of cargoes in vitro. Although promising, traditional cationic CPPs have some drawbacks that hinder their therapeutic application such as rapid proteolytic degradation and undesired interactions with the biological milieu. To overcome these limitations, this article details the discovery of a new class of noncharged cell-penetrating oligoTEAs (CPOTs) that undergo extensive and rapid cellular entry across different cell lines with low cytotoxicity. CPOTs outperform a widely used CPP, R9 peptide. This new class of highly efficient noncharged macromolecular transporters are distinct from their cationic counterparts and show strong promise for the intracellular delivery of hydrophilic small-molecule therapeutics.
细胞内药物递送系统通常受到其血清稳定性和递送效率差的限制。在这方面，细胞穿透肽（CPPs），特别是那些来源于碱性蛋白亚基的 CPPs，已经得到了广泛的研究，并被用于体外递送各种货物。尽管很有前途，但传统的阳离子 CPP 存在一些缺点，限制了它们的治疗应用，例如快速的蛋白水解降解和与生物环境的不期望相互作用。为了克服这些限制，本文详细介绍了一类新型的非带电细胞穿透寡 TEAs（CPOTs）的发现，它们能够在不同的细胞系中广泛而快速地进入细胞，同时具有低细胞毒性。CPOTs 的性能优于广泛使用的 CPP，R9 肽。这种新型高效的非带电大分子转运体与阳离子同类物不同，为亲水性小分子治疗剂的细胞内递送提供了很大的希望。
