Surface-enhanced Raman spectroscopy based 3D spheroid culture for drug discovery studies

Altunbek, Mine; Çetin, Demet; Suludere, Zekiye; Çulha, Mustafa

doi:10.1016/j.talanta.2018.08.087

Cited by 19 publications

(22 citation statements)

References 70 publications

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“…Finally, light scattering in thick tissue hampers resolution and sensitivity of optical technologies, such as Ca 2+ confocal microscopy, nanoparticles with fluorescent reporters or biosensing methods based on surface‐enhanced Raman scattering. [ 13 ] Besides, without slicing the 3D model, optic‐based technologies are limited to measures on the superficial, outer layer of the sample, and are subject to alignment issues which makes them unpractical to study large number of samples.…”

Section: Introductionmentioning

confidence: 99%

Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

et al. 2020

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diseases and develop potential cures. [1] Developments across the fields of biotechnology, tissue engineering, biomaterials, and microtechnology, have led to in vitro models ranging from multilayer 3D cell cultures [2] to small self-standing cell aggregates called spheroids, [3] up to complex brain organoids derived from human pluripotent stem (hPS) cells. [4] Albeit grown in an artificial in vitro environment, the shift from conventional 2D neural cultures to 3D models was shown to better mimic the complexity of intertwined 3D networks found in the brain. [5] hPS-derived brain organoids can indeed recapitulate several aspects specific to human brain development at the level of gene expression, [6] cell-type differentiation and network formation, [7] and can express phenotypes of human brain diseases when generated from patient-derived hPS-cells. [4a,8] Following these results, 3D neural cell assemblies have raised a large interest for the study of human brain diseases and therapies. Furthermore, these models can overcome certain limitations of currently used animal models, such as low experimental accessibility for functional studies, [9] low sample size, low reproducibility and, above all, poor translational relevance of screening results to humans. [5] The routine experimental use of 3D brain tissue models, however, remains largely unpractical for applications in drugdiscovery. On one side, intermodel variability and unmonitored cellular viability can affect the reliable generation of complex 3D brain tissue model systems. For instance, as 3D models become critically sized, the low diffusion of nutrients and oxygen tends to induce the formation of a necrotic core, [1b,4a,5] with consequent losses in cellular viability. On the other side, available biosensing technologies are not yet adapted for the routine monitoring of biosignals such as neural activity inside individual 3D models. This hinders studies aiming toward a better understanding of the emergence of spontaneous neural activity in these models as well as their optimization to reliably generate electrically active brain tissue models for functional assays. Over the last few years, researchers have been working on protocols for culturing organoids with minimal variability, mainly focusing on homogenizing morphologies. [4c] As far as monitoring brain organoids, current major biosensing Brain organoids is an exciting technology proposed to advance studies on human brain development, diseases, and possible therapies. Establishing and applying such models, however, is hindered by the lack of technologies to chronically monitor neural activity. A promising new approach comprising selfstanding biosensing microdevices capable of achieving seamless tissue integration during cell aggregation and culture. To date, there is little information on how to control the aggregation of such bioartificial 3D neural assemblies. Here, the growth of hybrid neurospheroids obtained by the aggregation of silicon sham microchips (100 × 100 × 50 μm 3) with primary cortical cells ...

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Section: Introductionmentioning

confidence: 99%

Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

et al. 2020

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“…27 Moreover, Altunbek et al used SERS and the hanging drop method to monitor the cellular response to drug exposure. 28 …”

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confidence: 99%

Detection of Estrogen Receptor Alpha and Assessment of Fulvestrant Activity in MCF-7 Tumor Spheroids Using Microfluidics and SERS

et al. 2021

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Breast cancer is one of the leading causes of cancer death in women. Novel in vitro tools that integrate three-dimensional (3D) tumor models with highly sensitive chemical reporters can provide useful information to aid biological characterization of cancer phenotype and understanding of drug activity. The combination of surface-enhanced Raman scattering (SERS) techniques with microfluidic technologies offers new opportunities for highly selective, specific, and multiplexed nanoparticle-based assays. Here, we explored the use of functionalized nanoparticles for the detection of estrogen receptor alpha (ERα) expression in a 3D tumor model, using the ERα-positive human breast cancer cell line MCF-7. This approach was used to compare targeted versus nontargeted nanoparticle interactions with the tumor model to better understand whether targeted nanotags are required to efficiently target ERα. Mixtures of targeted anti-ERα antibody-functionalized nanotags (ERα-AuNPs) and nontargeted (against ERα) anti-human epidermal growth factor receptor 2 (HER2) antibody-functionalized nanotags (HER2-AuNPs), with different Raman reporters with a similar SERS signal intensity, were incubated with MCF-7 spheroids in microfluidic devices and spectroscopically analyzed using SERS. MCF-7 cells express high levels of ERα and no detectable levels of HER2. 2D and 3D SERS measurements confirmed the strong targeting effect of ERα-AuNP nanotags to the MCF-7 spheroids in contrast to HER2-AuNPs (63% signal reduction). Moreover, 3D SERS measurements confirmed the differentiation between the targeted and the nontargeted nanotags. Finally, we demonstrated how nanotag uptake by MCF-7 spheroids was affected by the drug fulvestrant, the first-in-class approved selective estrogen receptor degrader (SERD). These results illustrate the potential of using SERS and microfluidics as a powerful in vitro platform for the characterization of 3D tumor models and the investigation of SERD activity.

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“…This in turn gives constructive information regarding the stimuli-induced biochemical changes in the target cells. 59 F I G U R E 4 Techniques used for the analysis of 3D cultures can be broadly classified as microscopy, biosensors, microfluidics and elastography. The automated image analysis software such as FluoroCellTrack and CellProfiler help in assessing several endpoints such as spheroid morphology, ECM interactions and altered cellular profiles after drug administration.…”

Section: Surface-enhanced Raman Scattering (Sers)mentioning

confidence: 99%

Devices and techniques used to obtain and analyze three‐dimensional cell cultures

Agrawal

Ramesh

Aishwarya

et al. 2021

Biotechnology Progress

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Cell cultures are indispensable for both basic and applied research. Advancements in cell culture and analysis increase their utility for basic research and translational applications. A marked development in this direction is advent of three-dimensional (3D) cultures. The extent of advancement in 3D cell culture methods over the past decade has warranted referring to a single cell type being cultured as an aggregate or spheroid using simple scaffolds as "traditional." In recent years, the development of "next-generation" devices has enabled cultured cells to mimic their natural environments much better than the traditional 3D culture systems. Automated platforms like chip-based devices, magnetic-and acoustics-based assembly devices, dielectrophoresis (DEP), micro pocket cultures (MPoC), and 3D bio-printing provide a dynamic environment compared to the rather static conditions of the traditional simple scaffold-based 3D cultures. Chip-based technologies, which are centered on prin-

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Surface-enhanced Raman spectroscopy based 3D spheroid culture for drug discovery studies

Cited by 19 publications

References 70 publications

Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

Surface‐Functionalized Self‐Standing Microdevices Exhibit Predictive Localization and Seamless Integration in 3D Neural Spheroids

Detection of Estrogen Receptor Alpha and Assessment of Fulvestrant Activity in MCF-7 Tumor Spheroids Using Microfluidics and SERS

Devices and techniques used to obtain and analyze three‐dimensional cell cultures

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