Multicellular Tumor Spheroids in Nanomedicine Research: A Perspective

Rossi, Martina; Blasi, Paolo

doi:10.3389/fmedt.2022.909943

Cited by 15 publications

(18 citation statements)

References 54 publications

(58 reference statements)

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“…2D surfaces represent the most traditional platforms employed to culture cancer cells, while 3D milieus exemplify the new technical alternatives used to study the behavior of malignant cells in vitro. [23,[45][46][47] Concerning the use of soft 2D hydrogels to pre-condition cancer cells, since these have a similar elasticity to the tumor-like microcapsules (23 ± 3.0 kPa or 21 ± 2.0 kPa respectively; Figures 1B and 1C), this strategy was utilized to discern the respective (which was not certified by peer review) is the author/funder. All rights reserved.…”

Section: Resultsmentioning

confidence: 99%

When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-like Microcapsules

Buehler

Krueger

Monavari

et al. 2022

Preprint

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In this work, we studied the generation and rising of polyploid cancer cells as a product of mechanical stress. To this purpose, MCF7 breast cancer cells were cultured on 2D (i.e. flasks, or flat hydrogels), and in 3D milieus (i.e. Spheroids, or immobilized within alginate-gelatin microbeads, named in this work as tumor-like microcapsules), and further analyzed by biophysical and genetic methods (i.e. single-cell Traction Force Microscopy and RNA-seq respectively). Our results show that MCF7 cells preconditioned onto 2D surfaces exhibit a low number of polynucleated cells, while their culture in 3D environments triggered their progressive generation with time. Genetic studies enabled us to determine that polyploid cells found in tumor-like microcapsules are likely originated by cell-cell fusion and disrupted cytokinesis, showing most of the genetic markers for Polyploid Giant Cancer Cell, while cells cultured as spheroids seem to be likely generated by other mechanisms, such as cell cannibalisms, entosis, or emperipolesis. Our outcomes strongly suggest that both mechanical stress and confinement are required to stimulate cell polyploidy, which can be easily addressed by the immobilization of breast cancer cells in tumor-like microcapsules.

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Section: Resultsmentioning

confidence: 99%

When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-like Microcapsules

Buehler

Krueger

Monavari

et al. 2022

Preprint

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“…It was found in studies that these types of spheroids show variations in cancer cells such as growth rate, morphology, and thickness of the cell wall which correlates with the characteristics of those cells in in vivo conditions. This technique’s major limitation can be resolved by using 96-well plates where single spheroid cells can be obtained [ 18 ]. Bioreactor system: this type of cell culture can be employed to produce the mass quantity of cells where the spheroids produced are heterogenous in size, shape, and cell population.…”

Section: Different Types Of Preclinical Cell Culture Modelsmentioning

confidence: 99%

Role of three-dimensional cell culture in therapeutics and diagnostics: an updated review

Biju

Priya

Francis

2023

Drug Deliv. and Transl. Res.

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Drug development and testing are a tedious and expensive process with a high degree of uncertainty in the clinical success and preclinical validation of manufactured therapeutic agents. Currently, to understand the drug action, disease mechanism, and drug testing, most therapeutic drug manufacturers use 2D cell culture models to validate the drug action. However, there are many uncertainties and limitations with the conventional use of 2D (monolayer) cell culture models for drug testing that are primarily attributed due to poor mimicking of cellular mechanisms, disturbance in environmental interaction, and changes in structural morphology. To overcome such odds and difficulties in the preclinical validation of therapeutic medications, newer in vivo drug testing cell culture models with higher screening efficiencies are required. One such promising and advanced cell culture model reported recently is the “three-dimensional cell culture model.” The 3D cell culture models are reported to show evident benefits over conventional 2D cell models. This review article outlines and describes the current advancement in cell culture models, their types, significance in high-throughput screening, limitations, applications in drug toxicity screening, and preclinical testing methodologies to predict in vivo efficacy. Graphical Abstract

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“…A spheroid is a 3D in vitro cell model used to mimic the structure of small avascular tumors. Several spheroid formation techniques have been developed [ 11 , 13 , 14 , 15 , 41 ], which can be roughly separated in two categories: scaffold-based and scaffold-free. In scaffold-based approaches, spheroids grow within a natural/synthetic matrix such as Matrigel ® (Corning Life Sciences, New York, NY, USA), collagen, agarose, etc.…”

Section: Spheroid Modelsmentioning

confidence: 99%

“…The first advantage of spheroids is their ability to mimic the characteristics of small avascular tumors by forming a sphere of tumor cells. In this configuration, only part of cells, in the periphery, are directly in contact with a medium and thus with drug/NPs, while most cells are hidden within the spheroid, escaping direct contact with environment [ 15 ]. Furthermore, spheroids can simulate cellular heterogeneity as found in tumors [ 11 , 41 ].…”

Section: Spheroid Modelsmentioning

confidence: 99%

“…However, before moving towards animal models, most of these studies could have been carried out on 3D in vitro models such as spheroids. A spheroid is a 3D model which recapitulates the structure of small avascular tumors [ 11 , 12 , 13 , 14 , 15 ]. By forming a sphere of cancerous cells, certain parameters specific to small avascular tumors can be simulated, such as the existence of oxygen, nutrients, and pH gradients, and the stratification of cells as proliferative periphery, quiescent area, and necrotic core.…”

Section: Introductionmentioning

confidence: 99%

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Quantum Dots Mediated Imaging and Phototherapy in Cancer Spheroid Models: State of the Art and Perspectives

et al. 2022

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Quantum Dots (QDs) are fluorescent nanoparticles known for their exceptional optical properties, i.e., high fluorescence emission, photostability, narrow emission spectrum, and broad excitation wavelength. These properties make QDs an exciting choice for bioimaging applications, notably in cancer imaging. Challenges lie in their ability to specifically label targeted cells. Numerous studies have been carried out with QDs coupled to various ligands like peptides, antibodies, aptamers, etc., to achieve efficient targeting. Most studies were conducted in vitro with two-dimensional cell monolayers (n = 8902) before evolving towards more sophisticated models. Three-dimensional multicellular tumor models better recapitulate in vivo conditions by mimicking cell-to-cell and cell-matrix interactions. To date, only few studies (n = 34) were conducted in 3D in vitro models such as spheroids, whereas these models could better represent QDs behavior in tumors compared to monolayers. Thus, the purpose of this review is to present a state of the art on the studies conducted with Quantum Dots on spheroid models for imaging and phototherapy purposes.

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Multicellular Tumor Spheroids in Nanomedicine Research: A Perspective

Cited by 15 publications

References 54 publications

When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-like Microcapsules

When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-like Microcapsules

Role of three-dimensional cell culture in therapeutics and diagnostics: an updated review

Quantum Dots Mediated Imaging and Phototherapy in Cancer Spheroid Models: State of the Art and Perspectives

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