Shape and surface modification dependent cellular interactions of gold nanoparticles in a 3D blood-brain-barrier supported neurospheroid model

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-12 DOI:10.1016/j.tice.2025.103080

Aysel Tomak , Pelin Saglam-Metiner , Reyhan Coban , Ceyda Oksel-Karakus , Ozlem Yesil-Celiktas

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引用次数: 0

Abstract

Recent investigations have begun to explore the cellular interactions of nanoparticles (NPs) in three-dimensional (3D) neuro-spheroid models of the blood-brain barrier (BBB), offering novel insights into NP transport across the barrier and their potential neurotoxic effects. Building on these findings, we investigated the effects of particle shape and surface modification on the transport dynamics and cellular interactions of gold NPs (AuNPs) using a multicellular 3D spheroid model of the BBB. AuNPs with two different morphologies, spherical and rod-like, were synthesized, modified with polyethylene glycol (PEG) and characterized in detail using Ultraviolet-Visible (UV-Vis) Spectroscopy, Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) techniques. A 3D neuro-spheroid model consisting of mouse brain endothelial cells (bEnd.3), motor neuron-like hybrid cells (NSC-34) and glial cells (C6) was employed to evaluate the BBB transport characteristics and cytotoxicity of bare and PEG-coated spherical and rod-shaped AuNPs. Our results indicated that 3D neurospheroid models can serve as orchestral platforms for studying cellular behaviour of NPs. PEGylation of NPs substantially reduced cytotoxic effects compared to bare particles. While spherical AuNPs showed limited translocation through the endothelial barrier, those that entered the spheroid were found to be distributed deeper within the interior. In contrast, rod-shaped particles exhibited a greater capacity to cross the BBB but tended to accumulate near the periphery without deeper penetration. These findings underscore the critical role of shape and surface chemistry in nanoparticle-mediated BBB transport and support the utility of 3D neuro-spheroid models in predicting nanoparticle behavior in brain tissue.

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在三维血脑屏障支持的神经球模型中，形状和表面修饰依赖于金纳米颗粒的细胞相互作用

最近的研究已经开始在血脑屏障（BBB）的三维（3D）神经球体模型中探索纳米颗粒（NPs）的细胞相互作用，为NP通过屏障的运输及其潜在的神经毒性作用提供了新的见解。基于这些发现，我们利用血脑屏障的多细胞3D球体模型研究了颗粒形状和表面修饰对金NPs （AuNPs）的运输动力学和细胞相互作用的影响。合成了球状和棒状两种不同形态的AuNPs，用聚乙二醇（PEG）修饰，并利用紫外可见光谱（UV-Vis）、扫描电子显微镜（SEM）、动态光散射（DLS）和电感耦合等离子体质谱（ICP-MS）技术对其进行了详细的表征。采用由小鼠脑内皮细胞（ben .3）、运动神经元样杂交细胞（NSC-34）和胶质细胞（C6）组成的三维神经球体模型，评估裸和peg包被的球形和杆状AuNPs的血脑卒中转运特性和细胞毒性。我们的研究结果表明，三维神经球模型可以作为研究NPs细胞行为的管弦乐平台。与裸粒子相比，聚乙二醇化大大降低了NPs的细胞毒性作用。虽然球形AuNPs通过内皮屏障的易位有限，但发现进入球体的AuNPs在内部分布较深。相反，杆状颗粒表现出更大的穿过血脑屏障的能力，但倾向于在周围积聚，而没有更深的穿透。这些发现强调了形状和表面化学在纳米颗粒介导的血脑屏障运输中的关键作用，并支持3D神经球体模型在预测纳米颗粒在脑组织中的行为方面的实用性。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.