Supramolecular polymers are attractive scaffolds for use as nanocarriers in drug delivery thanks to their modularity and easy fabrication; however, a molecular view into their in vivo behavior is lacking. Herein, we prepare fluorescent squaramide-based supramolecular polymer nanoparticles that range from fibers to spheres while maintaining their surface chemistry and near-neutral surface charge by a co-assembly approach involving a sulfo-cyanine-labeled monomer to track their in vivo biodistribution behavior and clearance in optically transparent zebrafish embryos. Evasion of macrophages, localization of the fibrillar aggregates in the caudal vein, and association with scavenger endothelial cells are observed. The interaction of the fibrillar supramolecular nanoparticles with the caudal vein is abrogated in gene-edited zebrafish lacking Stabilin-2, a receptor analogously found in the mammalian liver, providing a molecular view into their interaction with scavenger endothelial cells. We further show that this interaction can be tuned based on the choice of monomer and its resultant self-assembly.

中文翻译：

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Stab2 介导的斑马鱼胚胎中超分子聚合物纳米颗粒的清除。

由于其模块化和易于制造，超分子聚合物是用作药物输送纳米载体的有吸引力的支架；然而，缺乏对其体内行为的分子观察。在此，我们制备了基于荧光角酰胺的超分子聚合物纳米粒子，其范围从纤维到球体，同时通过涉及磺基花青标记单体的共组装方法保持其表面化学和近中性表面电荷，以跟踪它们在体内的生物分布行为和光学透明斑马鱼胚胎中的间隙。观察到巨噬细胞的逃逸、纤维状聚集体在尾静脉中的定位以及与清道夫内皮细胞的关联。在缺乏 Stabilin-2 的基因编辑斑马鱼中，纤维状超分子纳米粒子与尾静脉的相互作用被消除，一种在哺乳动物肝脏中类似发现的受体，为它们与清道夫内皮细胞的相互作用提供了分子视角。我们进一步表明，可以根据单体的选择及其产生的自组装来调整这种相互作用。