Evaluating nanoparticle localisation in glioblastoma multicellular tumour spheroids by surface enhanced Raman scattering.
Evaluating nanoparticle localisation in glioblastoma multicellular tumour spheroids by surface enhanced Raman scattering.
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DOI：
10.1039/d3an00751k
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发表时间：
2023-07-10
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多形性胶质母细胞瘤（GBM）是一种侵袭性极强的高级别脑癌，预后和预期寿命较差，迫切需要新的治疗方法。使用传统成像技术区分癌组织和非癌组织的困难加剧了这些严重的结果。金属纳米颗粒（NP）由于其不同的光学和物理性质而具有优势，例如其靶向和成像潜力。在这项工作中，吸收，分布和位置的二氧化硅包覆的金纳米粒子（金纳米粒子）内的多细胞肿瘤球体（MTS）来自U87-MG胶质母细胞瘤细胞的表面增强拉曼散射（Sers）光学映射进行了研究。MTS是三维体外肿瘤模拟物，其比二维细胞培养物更接近地代表体内肿瘤。通过使用AuNP-SHIN纳米标签，可以容易地用拉曼报告子功能化内部金表面，并且用抗体功能化外部二氧化硅表面以用于肿瘤特异性靶向。纳米标签被设计成靶向在U87-MG胶质母细胞瘤细胞中过表达的生物标志物生腱蛋白-C。免疫化学表明，生腱蛋白-C在MTS的核心内上调，然而诸如NP大小、静止和缺氧的限制限制了纳米标签对核心的渗透，并且它们保留在球状体的外部增殖细胞中。使用Sers的MTS研究的先前实例证明了NP在2D单层细胞上的孵育，随后从这些预孵育的细胞形成MTS。在这里，我们专注于本地化的纳米粒子孵育到预先形成的MTS后，建立一个更好的理解的目标和NP的吸收。因此，这项工作突出了NP摄取到这些3D体外模型中的研究和翻译的重要性。结合Sers和免疫组织化学提供了更深入的了解金纳米粒子如何分布在体外3D MTS模型。
Glioblastoma multiforme (GBM) is a particularly aggressive and high-grade brain cancer, with poor prognosis and life expectancy, in urgent need of novel therapies. These severe outcomes are compounded by the difficulty in distinguishing between cancerous and non-cancerous tissues using conventional imaging techniques. Metallic nanoparticles (NPs) are advantageous due to their diverse optical and physical properties, such as their targeting and imaging potential. In this work, the uptake, distribution, and location of silica coated gold nanoparticles (AuNP-SHINs) within multicellular tumour spheroids (MTS) derived from U87-MG glioblastoma cells was investigated by surface enhanced Raman scattering (SERS) optical mapping. MTS are three-dimensional in vitro tumour mimics that represent a tumour in vivo much more closely than that of a two-dimensional cell culture. By using AuNP-SHIN nanotags, it is possible to readily functionalise the inner gold surface with a Raman reporter, and the outer silica surface with an antibody for tumour specific targeting. The nanotags were designed to target the biomarker tenascin-C overexpressed in U87-MG glioblastoma cells. Immunochemistry indicated that tenascin-C was upregulated within the core of the MTS, however limitations such as NP size, quiescence, and hypoxia, restricted the penetration of the nanotags to the core and they remained in the outer proliferating cells of the spheroids. Previous examples of MTS studies using SERS demonstrated the incubation of NPs on a 2D monolayer of cells, with the subsequent formation of the MTS from these pre-incubated cells. Here, we focus on the localisation of the NPs after incubation into pre-formed MTS to establish a better understanding of targeting and NP uptake. Therefore, this work highlights the importance for the investigation and translation of NP uptake into these 3D in vitro models. Combining SERS and immunohistochemistry provides greater insight into how AuNPs distribute in in vitro 3D MTS models.
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影响因子：
--
作者：
Däster S;Amatruda N;Calabrese D;Ivanek R;Turrini E;Droeser RA;Zajac P;Fimognari C;Spagnoli GC;Iezzi G;Mele V;Muraro MG
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Muraro MG
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5
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影响因子：
8.4
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Faulds K
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Lingasamy, Prakash;Tobi, Allan;Teesalu, Tambet
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Teesalu, Tambet