Introduction: Humans are intentionally exposed to gold nanoparticles (AuNPs) where they are used in variety of biomedical applications as imaging and drug delivery agents as well as diagnostic and therapeutic agents currently in clinic and in a variety of upcoming clinical trials. Consequently, it is critical that we gain a better understanding of how physiochemical properties such as size, shape, and surface chemistry drive cellular uptake and AuNP toxicity in vivo. Understanding and being able to manipulate these physiochemical properties will allow for the production of safer and more efficacious use of AuNPs in biomedical applications.
Methods and Materials: Here, AuNPs of three sizes, 5 nm, 10 nm, and 20 nm, were coated with a lipid bilayer composed of sodium oleate, hydrogenated phosphatidylcholine, and hexanethiol. To understand how the physical features of AuNPs influence uptake through cellular membranes, sum frequency generation (SFG) was utilized to assess the interactions of the AuNPs with a biomimetic lipid monolayer composed of a deuterated phospholipid 1.2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (dDPPC).
Results and Discussion: SFG measurements showed that 5 nm and 10 nm AuNPs are able to phase into the lipid monolayer with very little energetic cost, whereas, the 20 nm AuNPs warped the membrane conforming it to the curvature of hybrid lipid-coated AuNPs. Toxicity of the AuNPs were assessed in vivo to determine how AuNP curvature and uptake influence cell health. In contrast, in vivo toxicity tested in embryonic zebrafish showed rapid toxicity of the 5 nm AuNPs, with significant 24 hpf mortality occurring at concentrations ≥ 20 mg/L, whereas the 10 nm and 20 nm AuNPs showed no significant mortality throughout the five-day experiment.
Conclusion: By combining information from membrane models using SFG spectroscopy with in vivo toxicity studies, a better mechanistic understanding of how nanoparticles (NPs) interact with membranes is developed to understand how the physiochemical features of AuNPs drive nanoparticle–membrane interactions, cellular uptake, and toxicity.

Keywords: gold nanoparticle, vibrational spectroscopy, nanoparticle–biological interactions, hybrid lipid-coated nanoparticle, toxicity, size-dependent interaction, zebrafish


中文翻译：

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脂质涂层金纳米粒子的尺寸依赖性相互作用：通过模型细胞膜和体内毒性发展更好的机制理解。

简介：人类有意暴露于金纳米粒子 (AuNPs)，它们在各种生物医学应用中用作成像和药物递送剂，以及目前临床和各种即将进行的临床试验中的诊断和治疗剂。因此，我们必须更好地了解物理化学特性（如大小、形状和表面化学）如何驱动细胞摄取和体内 AuNP 毒性。了解并能够操纵这些物理化学特性将允许在生物医学应用中更安全、更有效地使用金纳米粒子。
方法和材料：在这里，三种尺寸（5 nm、10 nm 和 20 nm）的 AuNPs 被涂有由油酸钠、氢化磷脂酰胆碱和己硫醇组成的脂质双层。为了了解 AuNPs 的物理特征如何影响细胞膜的吸收，利用和频生成 (SFG) 来评估 AuNPs 与由氘化磷脂 1.2-dipalmitoyl-d62-sn-glycero-3 组成的仿生脂质单层的相互作用-磷酸胆碱（dDPPC）。
结果与讨论：SFG 测量表明，5 nm 和 10 nm AuNPs 能够以很少的能量成本逐步进入脂质单层，而 20 nm AuNPs 使膜变形，使其符合混合脂质包被的 AuNPs 的曲率。在体内评估 AuNP 的毒性以确定 AuNP 曲率和摄取如何影响细胞健康。相比之下，在斑马鱼胚胎中测试的体内毒性显示 5 nm AuNPs 的快速毒性，在浓度 ≥ 20 mg/L 时发生显着的 24 hpf 死亡率，而 10 nm 和 20 nm AuNPs 在整个五天内没有显着死亡率实验。
结论：通过将使用 SFG 光谱的膜模型信息与体内毒性研究相结合，可以更好地理解纳米粒子 (NPs) 如何与膜相互作用，以了解 AuNPs 的物理化学特征如何驱动纳米粒子-膜相互作用、细胞摄取和毒性。

关键词：金纳米颗粒，振动光谱，纳米颗粒-生物相互作用，混合脂质包覆纳米颗粒，毒性，尺寸依赖性相互作用，斑马鱼