Spheroids as a Type of Three-Dimensional Cell Cultures—Examples of Methods of Preparation and the Most Important Application

Białkowska, Kamila; Komorowski, Piotr; Bryszewska, Maria; Miłowska, Katarzyna

doi:10.3390/ijms21176225

Cited by 237 publications

(181 citation statements)

References 79 publications

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“…Nanomaterials, e.g., dendrimers, are promising as siRNA carriers in gene silencing during gene therapy [5,[28][29][30]. For the first time, carbosilane dendrimers have been characterized as good carriers for siRNA by Weber et al [31].…”

Section: Discussionmentioning

confidence: 99%

Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells

Białkowska

Miłowska

Michlewska

et al. 2021

IJMS

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The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.

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Section: Discussionmentioning

confidence: 99%

Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells

Białkowska

Miłowska

Michlewska

et al. 2021

IJMS

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“…Cells are mostly cultured in monolayers (2D), and this cell environment may have an effect on the cellular response to external agents, e.g., drugs, and affect their cytotoxicity results [73]. Thus, we also performed analyses using the 3D cell cultures (spheroids), which mimic the natural microenvironment of growing tumor (TME), provide spatial cell-cell and cell-ECM (extracellular matrix) interactions [74], and also access the significantly stronger effects of therapeutics as compared to the response in 2D cultures [75].…”

Section: Discussionmentioning

confidence: 99%

Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

et al. 2021

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Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative—7-deazaKR—with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity.

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“…Various cancer cells can spontaneously assemble into spheroids in culture environment that privileges cell-cell and cell-ECM interactions over cell-substrate interactions [14]. These predominant cell-cell and cell-ECM interactions result in the formation of a 3D structure that closely reproduces mimics the native spatial organization and environment of avascular tumors, where cells can proliferate, aggregate and differentiate (Figure 2) [56].…”

Section: Common Characteristics Of Spheroids and Tumorsmentioning

confidence: 99%

“…Therefore, the development of preclinical models that better recapitulate patient tumor and microenvironment represents a promising challenge to improve the success rates in anticancer drug development. Since the discovery of the importance of the extracellular matrix (ECM) in cell behavior, it became clear that three-dimensional (3D) cell culture systems offer an excellent opportunity to recapitulate the real avascular tumor, by allowing cancer cells to be cultured, either alone or in co-culture with other cell types, in a spatial manner reminiscent of the structural architecture of the tumor that provides cell-cell and cell-ECM interactions, thereby mimicking the native tumor microenvironment (Table 1) [12][13][14][15]. Hopefully, besides circumventing the barriers and limitations imposed by 2D monolayer cultures, 3D cell culture models could reduce or, ideally, replace the use of animal models, thereby resolving the associated ethical and cost issues [16,17].…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research

et al. 2020

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Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell–cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.

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Spheroids as a Type of Three-Dimensional Cell Cultures—Examples of Methods of Preparation and the Most Important Application

Cited by 237 publications

References 79 publications

Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells

Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells

Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research

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