Comparative Study of the Cellular Uptake and Intracellular Behavior of a Library of Cyclic Peptide–Polymer Nanotubes with Different Self-Assembling Properties,Biomacromolecules

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Comparative Study of the Cellular Uptake and Intracellular Behavior of a Library of Cyclic Peptide–Polymer Nanotubes with Different Self-Assembling Properties
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-12-22 , DOI: 10.1021/acs.biomac.0c01512
Sean H Ellacott ₁ , Carlos Sanchez-Cano _{1,

2} , Edward D H Mansfield ₁ , Julia Y Rho ₁ , Ji-Inn Song ₁ , Raoul Peltier ₁ , Sébastien Perrier _{1,

3,

4}

Affiliation

Particle shape has been described as a key factor in improving cell internalization and biodistribution among the different properties investigated for drug-delivery systems. In particular, tubular structures have been identified as promising candidates for improving drug delivery. Here, we investigate the influence of different design elements of cyclic peptide–polymer nanotubes (CPNTs) on cellular uptake including the nature and length of the polymer and the cyclic peptide building block. By varying the composition of these cyclic peptide–polymer conjugates, a library of CPNTs of lengths varying from a few to over a 150 nm were synthesized and characterized using scattering techniques (small-angle neutron scattering and static light scattering). In vitro studies with fluorescently labeled CPNTs have shown that nanotubes comprised of a single polymer arm with a size between 8 and 16 nm were the most efficiently taken up by three different mammalian cell lines. A mechanistic study on multicellular tumor spheroids has confirmed the ability of these compounds to penetrate to their core. Variations in the proportion of paracellular and transcellular uptake with the self-assembling potential of the CPNT were also observed, giving key insights about the behavior of CPNTs in cellular systems.

中文翻译：

具有不同自组装特性的环状肽-聚合物纳米管库的细胞吸收和细胞内行为的比较研究

颗粒形状已被描述为在研究药物递送系统的不同特性之间改善细胞内在化和生物分布的关键因素。特别地，管状结构已被确认为改善药物递送的有希望的候选者。在这里，我们研究了环状肽-聚合物纳米管（CPNT）的不同设计元素对细胞吸收的影响，包括聚合物的性质和长度以及环状肽的基本组成部分。通过改变这些环状肽-聚合物共轭物的组成，合成了长度从几纳米到超过150 nm的CPNT库，并使用散射技术（小角度中子散射和静态光散射）对其进行了表征。用荧光标记的CPNT进行的体外研究表明，由大小为8至16 nm的单个聚合物臂组成的纳米管被三种不同的哺乳动物细胞系吸收的最有效。对多细胞肿瘤球体的机械研究已证实这些化合物能够渗透至其核心。还观察到副细胞和跨细胞摄取比例随CPNT自组装潜力的变化，从而提供了有关CPNT在细胞系统中行为的关键见解。

更新日期：2021-02-08

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