Low-dose albumin-coated gold nanorods induce intercellular gaps on vascular endothelium by causing the contraction of cytoskeletal actin
Low-dose albumin-coated gold nanorods induce intercellular gaps on vascular endothelium by causing the contraction of cytoskeletal actin
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DOI：
10.1016/j.jcis.2023.06.154
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发表时间：
2023-06-28
影响因子：
9.9
通讯作者：
Wang，Congzhou
中科院分区：
文献类型：
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作者：
Li，Zhengqiang;Liu，Jinyuan;Wang，Congzhou
通常通过基于生物化学的测定来评估纳米颗粒的细胞毒性，通常忽略细胞生物物理性质，例如细胞形态和细胞骨架肌动蛋白，其可以作为细胞毒性的更敏感的指标。在这里，我们证明，低剂量白蛋白包被的金纳米棒（HSA@AuNRs），虽然被认为是非细胞毒性的多种生化测定，可以诱导细胞间的差距，并提高人主动脉内皮细胞（HAECs）之间的细胞旁渗透性。细胞间隙的形成可归因于细胞形态和细胞骨架肌动蛋白结构的改变，如使用荧光染色、原子力显微镜和超分辨率成像在单层和单细胞水平上验证的。分子机制研究表明，HSA@AuNRs的胞吞作用可诱导HAECs内钙离子内流，激活肌动球蛋白收缩。考虑到内皮完整性/功能障碍在各种生理/病理条件下的重要作用，这项工作表明白蛋白涂层的金纳米棒对心血管系统的潜在不良影响。另一方面，这项工作也提供了一种可行的方式来调节内皮细胞的渗透性，从而促进药物和纳米颗粒的输送通过内皮。
Cytotoxicity of nanoparticles, typically evaluated by biochemical-based assays, often overlook the cellular biophysical properties such as cell morphology and cytoskeletal actin, which could serve as more sensitive indicators for cytotoxicity. Here, we demonstrate that low-dose albumin-coated gold nanorods (HSA@AuNRs), although being considered noncytotoxic in multiple biochemical assays, can induce intercellular gaps and enhance the paracellular permeability between human aortic endothelial cells (HAECs). The formation of intercellular gaps can be attributed to the changed cell morphology and cytoskeletal actin structures, as validated at the monolayer and single cell levels using fluorescence staining, atomic force microscopy, and super-resolution imaging. Molecular mechanistic study shows the caveolae-mediated endocytosis of HSA@AuNRs induces the calcium influx and activates actomyosin contraction in HAECs. Considering the important roles of endothelial integrity/dysfunction in various physiological/pathological conditions, this work suggests a potential adverse effect of albumin-coated gold nanorods on the cardiovascular system. On the other hand, this work also offers a feasible way to modulate the endothelial permeability, thus promoting drug and nanoparticle delivery across the endothelium.