Cancer progression is associated with overexpression of various receptors at the cell surface. Among these, CD44 is known to recognize and bind specifically hyaluronan (HA) and interact with less affinity to other glycosaminoglycans (GAGs), such as chondroitin sulfate (CS). In this study, we describe a simple method to obtain micellar nanoparticles with a GAG shell (HA or CS) as potential drug delivery systems that target cancer cells overexpressing CD44. Alkanethiol was conjugated at the reducing end of the respective GAG using highly efficient oxime chemistry. The alkane moiety confers amphiphilic behavior to the obtained conjugates and triggers their self-assembly into micellar nanoparticles, while the thiol group adds redox-responsiveness to the system. The properties of the particles depend on the used GAG: HA amphiphiles form more dense, smaller assemblies that are redox sensitive. Both systems allow encapsulation of either hydrophobic or hydrophilic cargos with high efficiency. We demonstrate that the GAGs exposed on the surface of the nanoparticles are with preserved bioactivity and recognized by the cellular receptors: the particles were internalized via CD44 dependent pathways.

中文翻译：

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糖胺聚糖对CD44靶向药物传递的氧化还原反应性胶束纳米颗粒。

癌症进展与细胞表面各种受体的过度表达有关。其中，已知CD44能特异性识别并结合透明质酸（HA），并且与其他糖胺聚糖（GAG），例如硫酸软骨素（CS）的亲和力较小。在这项研究中，我们描述了一种简单的方法来获得具有GAG壳（HA或CS）的胶束纳米粒子，作为靶向潜在的过度表达CD44癌细胞的药物递送系统。使用高效的肟化学方法将链烷醇偶联在各自GAG的还原端。烷烃部分赋予所获得的结合物两亲性，并触发其自组装成胶束纳米粒子，而巯基则为系统增加了氧化还原反应性。颗粒的性质取决于所用的GAG：HA两亲物形成的密度更高，对氧化还原敏感的较小的程序集。两种系统都可以高效地包裹疏水性或亲水性货物。我们证明暴露在纳米粒子表面上的GAG具有保留的生物活性，并被细胞受体识别：粒子通过CD44依赖性途径被内化。