Size-Dependent Interactions of Lipid-Coated Gold Nanoparticles: Developing a Better Mechanistic Understanding Through Model Cell Membranes and in vivo Toxicity
Size-Dependent Interactions of Lipid-Coated Gold Nanoparticles: Developing a Better Mechanistic Understanding Through Model Cell Membranes and in vivo Toxicity
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DOI：
10.2147/ijn.s249622
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发表时间：
2020-01-01
影响因子：
8
通讯作者：
Harper, Stacey L.
中科院分区：
文献类型：
--
作者：
Engstrom, Arek M.;Faase, Ryan A.;Harper, Stacey L.
简介：人类故意暴露于金纳米颗粒（AuNPs），其中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在临床和各种即将进行的临床试验中的诊断和治疗剂。因此，至关重要的是，我们更好地了解物理化学性质，如大小，形状和表面化学如何驱动体内细胞摄取和AuNP毒性。理解和能够操纵这些物理化学性质将允许生产更安全，更有效地使用金纳米粒子在biomedical application.Methods和Materials：在这里，金纳米粒子的三个大小，5 nm，10 nm，和20 nm，涂有脂质双层组成的油酸钠，氢化磷脂酰胆碱，和hexanethelamine。为了理解AuNP的物理特征如何影响通过细胞膜的摄取，利用和频产生（SFG）来评估AuNP与由氘代磷脂1.2-二棕榈酰-d 62-sn-甘油基-3-磷酸胆碱（dDPPC）组成的仿生脂质单层的相互作用。SFG测量表明，5 nm和10 nm的金纳米粒子能够以非常少的能量成本相进入脂质单层，而20 nm的金纳米粒子使膜弯曲，使其符合混合脂质涂覆的金纳米粒子的曲率。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，在胚胎斑马鱼中测试的体内毒性显示5 nm AuNP的快速毒性，在浓度>= 20 mg/L时发生显著的24 hpf死亡率，而10 nm和20 nm AuNP在整个五天实验中没有显示显著的死亡率。通过将来自使用SFG光谱的膜模型的信息与体内毒性研究相结合，更好地理解纳米颗粒（NPs）如何与膜相互作用的机理，以理解AuNPs的理化特征如何驱动纳米颗粒-膜相互作用、细胞摄取和毒性。
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.