A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

Neto, Ana I.; Correia, Clara R.; Oliveira, Mariana B.; Rial-Hermida, M. Isabel; Alvarez‐Lorenzo, Carmen; Reis, Rui L.

doi:10.1039/c4bm00411f

Cited by 76 publications

(77 citation statements)

References 42 publications

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“…It is in a good agreement with the knowledge that necrotic core appears in spheroids which are larger than 400-500 µm in diameter. 44,45 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 -17 -…”

Section: Accumulation Of the Microcontainers In Multicellular Tumor Smentioning

confidence: 98%

Ultrasonically Assisted Polysaccharide Microcontainers for Delivery of Lipophilic Antitumor Drugs: Preparation and in Vitro Evaluation

Akasov

Bоrodinа

Zaytseva

et al. 2015

ACS Appl. Mater. Interfaces

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High toxicity, poor selectivity, and severe side effects are major drawbacks of anticancer drugs. Various drug delivery systems could be proposed to overcome these limitations. The aim of this study was to fabricate polysaccharide microcontainers (MCs) loaded with thymoquinone (TQ) by a one-step ultrasonication technique and to study their cellular uptake and cytotoxicity in vitro. Two MC fractions with a mean size of 500 nm (MC-0.5) and 2 μM (MC-2) were prepared and characterized. Uptake of the MCs by mouse melanoma M-3 cells was evaluated in both 2D (monolayer culture) and 3D (multicellular tumor spheroids) models by confocal microscopy, flow cytometry, and fluorimetry. The higher cytotoxicity of the TQ-MC-0.5 sample than the TQ-MC-2 fraction was in good correlation with higher MC-0.5 accumulation in the cells. The MC-0.5 beads were more promising than the MC-2 particles because of a higher cellular uptake in both 2D and 3D models, an enhanced antitumor effect, and a lower nonspecific toxicity.

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Section: Accumulation Of the Microcontainers In Multicellular Tumor Smentioning

confidence: 98%

Ultrasonically Assisted Polysaccharide Microcontainers for Delivery of Lipophilic Antitumor Drugs: Preparation and in Vitro Evaluation

Akasov

Bоrodinа

Zaytseva

et al. 2015

ACS Appl. Mater. Interfaces

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“…There are several methods for cell spheroid formation other than the microfluidic approach including magnetic levitation [34], 3D-bioprinting [35], hydrophobic surfaces [36], matrix-on-top [37], matrix-embedded [38], polymeric aqueous two-phase system [39], floating liquid marbles [40], multiwell plates [41], bioreactor flasks [42], liquid overlay [43] and HD techniques [36]. Some of these techniques such as HD and multiwell plates are laborious while some others like 3D-bioprinting and magnetic levitation are costly and still lack the standard protocols.…”

Section: Conventional Methods For Spheroid Formationmentioning

confidence: 99%

Inventions and Innovations in Preclinical Platforms for Cancer Research

2018

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Three-dimensional (3D) cell culture systems can be regarded as suitable platforms to bridge the huge gap between animal studies and two-dimensional (2D) monolayer cell culture to study chronic diseases such as cancer. In particular, the preclinical platforms for multicellular spheroid formation and culture can be regarded as ideal in vitro tumour models. The complex tumour microenvironment such as hypoxic region and necrotic core can be recapitulated in 3D spheroid configuration. Cells aggregated in spheroid structures can better illustrate the performance of anti-cancer drugs as well. Various methods have been proposed so far to create such 3D spheroid aggregations. Both conventional techniques and microfluidic methods can be used for generation of multicellular spheroids. In this review paper, we first discuss various spheroid formation phases. Then, the conventional spheroid formation techniques such as bioreactor flasks, liquid overlay and hanging droplet technique are explained. Next, a particular topic of the hydrogel in spheroid formation and culture is explored. This topic has received less attention in the literature. Hydrogels entail some advantages to the spheroid formation and culture such as size uniformity, the formation of porous spheroids or hetero-spheroids as well as chemosensitivity and invasion assays and protecting from shear stress. Finally, microfluidic methods for spheroid formation and culture are briefly reviewed.

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“…Several methods are used to generate 3-D multicellular tumor spheroids including: (i) Bioreactors(BRs) in which cells or spheroids aggregate in the chamber; [38][39][40] (ii) nonadherent plates that prevent attachment; 41,42 (iii) hanging-drop (HD) plates where cells are grown in a suspended droplet to form one single spheroid; [43][44][45][46] (iv) multicellular layers; [47][48][49] and (v) organoid culture 50,51 among others. In this paper, BDI was used to assess the different cellular responses to paclitaxel of cancer spheroids obtained by using the three most common approaches: BR, HD, and nonadherent plate growth.…”

Section: Methodsmentioning

confidence: 99%

Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture

Sun

Merrill

An³

et al. 2017

J. Biomed. Opt

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Abstract. Three-dimensional (3-D) tissue culture represents a more biologically relevant environment for testing new drugs compared to conventional two-dimensional cancer cell culture models. Biodynamic imaging is a highcontent 3-D optical imaging technology based on low-coherence interferometry and digital holography that uses dynamic speckle as high-content image contrast to probe deep inside 3-D tissue. Speckle contrast is shown to be a scaling function of the acquisition time relative to the persistence time of intracellular transport and hence provides a measure of cellular activity. Cellular responses of 3-D multicellular spheroids to paclitaxel are compared among three different growth techniques: rotating bioreactor (BR), hanging-drop (HD), and nonadherent (U-bottom, UB) plate spheroids, compared with ex vivo living tissues. HD spheroids have the most homogeneous tissue, whereas BR spheroids display large sample-to-sample variability as well as spatial heterogeneity. The responses of BR-grown tumor spheroids to paclitaxel are more similar to those of ex vivo biopsies than the responses of spheroids grown using HD or plate methods. The rate of mitosis inhibition by application of taxol is measured through tissue dynamics spectroscopic imaging, demonstrating the ability to monitor antimitotic chemotherapy. These results illustrate the potential use of low-coherence digital holography for 3-D pharmaceutical screening applications.

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A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

Cited by 76 publications

References 42 publications

Ultrasonically Assisted Polysaccharide Microcontainers for Delivery of Lipophilic Antitumor Drugs: Preparation and in Vitro Evaluation

Ultrasonically Assisted Polysaccharide Microcontainers for Delivery of Lipophilic Antitumor Drugs: Preparation and in Vitro Evaluation

Inventions and Innovations in Preclinical Platforms for Cancer Research

Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture

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