Understanding nanoparticle-cell interaction is essential for advancing research in nanomedicine and nanotoxicology. Apart from the transcytotic pathway mediated by cellular recognition and energetics, nanoparticles (including nanomedicines) may harness the paracellular route for their transport by inducing endothelial leakiness at cadherin junctions. This phenomenon, termed as NanoEL, is correlated with the physicochemical properties of the nanoparticles in close association with cellular signalling, membrane mechanics, as well as cytoskeletal remodelling. However, nanoparticles in biological systems are transformed by the ubiquitous protein corona and yet the potential effect of the protein corona on NanoEL remains unclear. Using confocal fluorescence microscopy, biolayer interferometry, transwell, toxicity, and molecular inhibition assays, complemented by molecular docking, here we reveal the minimal to significant effects of the anionic human serum albumin and fibrinogen, the charge neutral immunoglobulin G as well as the cationic lysozyme on negating gold nanoparticle-induced endothelial leakiness in vitro and in vivo. This study suggests that nanoparticle-cadherin interaction and hence the extent of NanoEL may be partially controlled by pre-exposing the nanoparticles to plasma proteins of specific charge and topology to facilitate their biomedical applications.

中文翻译：

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用蛋白冠控制纳米颗粒诱导的内皮渗漏

了解纳米颗粒-细胞相互作用对于推进纳米医学和纳米毒理学研究至关重要。除了细胞识别和能量学介导的转胞吞途径外，纳米颗粒（包括纳米药物）还可以通过诱导钙粘蛋白连接处的内皮渗漏来利用细胞旁途径进行运输。这种现象被称为 NanoEL，与纳米颗粒的物理化学性质相关，与细胞信号传导、膜力学以及细胞骨架重塑密切相关。然而，生物系统中的纳米粒子会被普遍存在的蛋白电晕转化，但蛋白电晕对 NanoEL 的潜在影响仍不清楚。使用共聚焦荧光显微镜、生物层干涉测量、transwell、毒性和分子抑制测定，并辅以分子对接，我们揭示了阴离子人血清白蛋白和纤维蛋白原、电荷中性免疫球蛋白 G 以及阳离子溶菌酶的最小到显着的影响在体外和体内消除金纳米粒子诱导的内皮渗漏。这项研究表明，纳米颗粒-钙粘蛋白相互作用以及 NanoEL 的程度可以通过将纳米颗粒预先暴露于特定电荷和拓扑的血浆蛋白来部分控制，以促进其生物医学应用。