Investigation of cellular uptake mechanism of functionalised gold nanoparticles into breast cancer using SERS.
Investigation of cellular uptake mechanism of functionalised gold nanoparticles into breast cancer using SERS.
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DOI：
10.1039/d0sc01255f
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发表时间：
2020-05-27
期刊：
影响因子：
8.4
通讯作者：
Faulds K
中科院分区：
文献类型：
--
作者：
Kapara A;Brunton V;Graham D;Faulds K
金纳米颗粒（AuNP）广泛用于癌症成像和药物输送等各种应用。AuNP的功能化已显示影响其细胞内化、积累和靶向效率。不同癌细胞对功能化AuNP的细胞摄取机制尚未完全了解。因此，有必要详细了解的分子过程，以提高金纳米粒子的选择性摄取和命运在特定的细胞系统。这些知识可以极大地帮助设计具有更高细胞摄取的纳米标签，以获得更具选择性和特异性的靶向能力，同时减少脱靶效应。在这里，我们首次展示了一种简单且非破坏性的3D表面增强拉曼光谱（Sers）成像方法，用于在不同条件下（包括温度和发动蛋白抑制）跟踪MCF-7 ERα阳性人乳腺癌细胞中抗ER α（雌激素受体α）抗体功能化的AuNP的细胞摄取和定位。3D Sers使得能够对Sers纳米标签的细胞内内化进行信息丰富的监测。研究发现，ERα-AuNP以温度依赖性方式被MCF-7细胞内化，这表明存在一种主动的胞吞依赖机制。3D Sers细胞作图还表明，纳米标签使用发动蛋白依赖性内吞作用进入MCF-7细胞，因为发动蛋白抑制导致Sers信号从细胞表面或接近细胞表面而不是细胞内部获得。最后，发现ERα-AuNPs通过ERα受体介导的内吞过程进入MCF-7细胞。这项研究讨论了Sers纳米标签在生物环境中的功能化作用，并强调了使用3D Sers研究细胞摄取过程的好处。使用灵敏，非破坏性和直接的3D Sers来研究整个细胞体积中功能化纳米标签的细胞摄取过程。
Gold nanoparticles (AuNPs) are widely used in various applications such as cancer imaging and drug delivery. The functionalisation of AuNPs has been shown to affect their cellular internalisation, accumulation and targeting efficiency. The mechanism of cellular uptake of functionalised AuNPs by different cancer cells is not well understood. Therefore, a detailed understanding of the molecular processes is necessary to improve AuNPs for their selective uptake and fate in specific cellular systems. This knowledge can greatly help in designing nanotags with higher cellular uptake for more selective and specific targeting capabilities with less off-target effects. Here, we demonstrate for the first time a straightforward and non-destructive 3D surface enhanced Raman spectroscopy (SERS) imaging approach to track the cellular uptake and localisation of AuNPs functionalised with an anti-ERα (estrogen receptor alpha) antibody in MCF-7 ERα-positive human breast cancer cells under different conditions including temperature and dynamin inhibition. 3D SERS enabled information rich monitoring of the intracellular internalisation of the SERS nanotags. It was found that ERα-AuNPs were internalised by MCF-7 cells in a temperature-dependent manner suggesting an active endocytosis-dependent mechanism. 3D SERS cell mapping also indicated that the nanotags entered MCF-7 cells using dynamin dependent endocytosis, since dynamin inhibition resulted in the SERS signal being obtained from, or close to, the cell surface rather than inside the cells. Finally, ERα-AuNPs were found to enter MCF-7 cells using an ERα receptor-mediated endocytosis process. This study addresses the role of functionalisation of SERS nanotags in biological environments and highlights the benefits of using 3D SERS for the investigation of cellular uptake processes. Use of sensitive, non-destructive and straightforward 3D SERS for investigating the cellular uptake processes of functionalised nanotags in entire cell volume.
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影响因子：
4.7
作者：
Albertazzi, Lorenzo;Fernandez-Villamarin, Marcos;Fernandez-Megia, Eduardo
通讯作者：
Fernandez-Megia, Eduardo
影响因子：
7.4
作者：
Craig, Derek;McAughtrie, Sarah;Graham, Duncan
通讯作者：
Graham, Duncan
影响因子：
--
作者：
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通讯作者：
Acconcia, Filippo
影响因子：
7.4
作者：
Haiss, Wolfgang;Thanh, Nguyen T. K.;Fernig, David G.
通讯作者：
Fernig, David G.
影响因子：
3.9
作者：
Gandubert, VJ;Lennox, RB
通讯作者：
Lennox, RB