Intracellular Delivery via Noncharged Sequence-Defined Cell-Penetrating Oligomers,Bioconjugate Chemistry

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Intracellular Delivery via Noncharged Sequence-Defined Cell-Penetrating Oligomers
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-06-28 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00336
Ngoc N. Phan ₁ , Connie Li ₁ , Christopher A. Alabi ₁

Affiliation

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.

中文翻译：

通过不带电的序列定义的细胞穿透寡聚体进行细胞内递送。

细胞内药物递送系统通常由于其较差的血清稳定性和递送效率而受到限制。细胞穿透肽（CPPs），特别是那些衍生自碱性蛋白亚基的肽，已经在这方面进行了广泛的研究，并用于体外递送多种货物。尽管有希望，但是传统的阳离子CPP具有一些缺点，这些缺点阻碍了它们的治疗应用，例如快速的蛋白水解降解以及与生物环境的不良相互作用。为了克服这些局限性，本文详细介绍了新型不带电的穿透细胞的寡聚TEA（CPOT）的发现，该寡聚TEA在细胞毒性低的情况下跨不同的细胞系进行了广泛而快速的细胞进入。CPOT胜过广泛使用的CPP R9肽。这类新型的高效不带电大分子转运蛋白不同于它们的阳离子对应物，显示出亲水小分子治疗药物在细胞内递送的强大前景。

更新日期：2018-06-28

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