Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB, The Netherlands.
Department of Biomedical Engineering, Laboratory for Cell and Tissue Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, The Netherlands.
J Mater Chem B. 2024 May 22;12(20):4854-4866. doi: 10.1039/d3tb02631k.
Intracellular delivery of functional biomolecules by using supramolecular polymer nanostructures has gained significant interest. Here, various charged supramolecular ureido-pyrimidinone (UPy)-aggregates were designed and formulated a simple "mix-and-match" method. The cellular internalization of these UPy-aggregates in the presence or absence of serum proteins by phagocytic and non-phagocytic cells, , THP-1 derived macrophages and immortalized human kidney cells (HK-2 cells), was systematically investigated. In the presence of serum proteins the UPy-aggregates were taken up by both types of cells irrespective of the charge properties of the UPy-aggregates, and the UPy-aggregates co-localized with mitochondria of the cells. In the absence of serum proteins only cationic UPy-aggregates could be effectively internalized by THP-1 derived macrophages, and the internalized UPy-aggregates either co-localized with mitochondria or displayed as vesicular structures. While the cationic UPy-aggregates were hardly internalized by HK-2 cells and could only bind to the membrane of HK-2 cells. With adding and increasing the amount of serum albumin in the cell culture medium, the cationic UPy-aggregates were gradually taken up by HK-2 cells without anchoring on the cell membranes. It is proposed that the serum albumin regulates the cellular internalization of UPy-aggregates. These results provide fundamental insights for the fabrication of supramolecular polymer nanostructures for intracellular delivery of therapeutics.
利用超分子聚合物纳米结构将功能性生物分子递送到细胞内已经引起了广泛的关注。在这里，我们设计并制备了各种带有电荷的超分子尿嘧啶嘧啶酮（UPy）聚集体，采用了一种简单的“混合匹配”方法。通过吞噬细胞和非吞噬细胞（THP-1 衍生的巨噬细胞和永生化人肾细胞（HK-2 细胞））系统地研究了这些 UPy 聚集体在有或没有血清蛋白存在的情况下的细胞内摄取情况。在有血清蛋白存在的情况下，无论 UPy 聚集体的电荷性质如何，这两种类型的细胞都能摄取 UPy 聚集体，并且 UPy 聚集体与细胞的线粒体共定位。在没有血清蛋白存在的情况下，只有阳离子 UPy 聚集体能够被 THP-1 衍生的巨噬细胞有效摄取，并且摄取的 UPy 聚集体要么与线粒体共定位，要么呈现出囊泡结构。而阳离子 UPy 聚集体则很难被 HK-2 细胞摄取，只能与 HK-2 细胞的细胞膜结合。随着细胞培养液中血清白蛋白的加入和增加，阳离子 UPy 聚集体逐渐被 HK-2 细胞摄取，而无需锚定在细胞膜上。据推测，血清白蛋白调节 UPy 聚集体的细胞内摄取。这些结果为制备用于治疗药物细胞内递药的超分子聚合物纳米结构提供了基础见解。
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