Three dimensional spheroid cell culture for nanoparticle safety testing

Sambale, Franziska; Lavrentieva, Antonina; Stahl, Frank; Blume, Cornelia; Stiesch, Meike; Kasper, Cornelia; Bahnemann, Detlef W.; Scheper, Thomas

doi:10.1016/j.jbiotec.2015.01.001

Cited by 78 publications

(67 citation statements)

References 33 publications

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“…S3). 22,46 Similar to our findings, conventional monolayer cell cultures being more sensitive against NPs or drug molecules in comparison to various 3D cell culture systems have been also reported by other groups. 38 NP-induced hormesis was attributed to increasing ROS levels with low-doses, giving rise to cell activities to suppress the imbalance, thus causing an increase in metabolic activities.…”

Section: Cell Viability Studiessupporting

confidence: 92%

Evaluation of CdTe/CdS/ZnS core/shell/shell quantum dot toxicity on three-dimensional spheroid cultures

Ulusoy

Lavrentieva

Walter

et al. 2015

Toxicology Research

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In this work, three-dimensional (3D) spheroid cultures of human adipose-derived mesenchymal stem cells (hAD-MSCs), with tissue-mimetic morphology through well developed cell-cell and cell-matrix interactions and distinct diffusion/transport characteristics, were assessed for dose-dependent toxic effects of red-emitting CdTe/CdS/ZnS quantum dots (Qdots). Morphological investigations and time-resolved microscopy analysis in addition to cell metabolic activity studies revealed that 3D spheroid cultures are more resistant to Qdot-induced cytotoxicity in comparison to conventional 2D cultures. The obtained results suggest the presence of two distinct cell populations in 2D cultures with different sensitivity to Qdots, however that effect wasn't observed in 3D spheroids. Our investigations were aimed to improve the prediction of nanotoxicity of Qdot on tissue-level and provide the essential screening steps prior to any application. Moreover, penetration ability of highly fluorescent Qdots to densely-packed spheroids will fortify the biological application of developed Qdots in tissue-like structures.

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Section: Cell Viability Studiessupporting

confidence: 92%

Evaluation of CdTe/CdS/ZnS core/shell/shell quantum dot toxicity on three-dimensional spheroid cultures

Ulusoy

Lavrentieva

Walter

et al. 2015

Toxicology Research

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“…Also with regard to ROS diffusion and PS penetration a 3D environment may be advantageous. Spheroids have thus been proposed not only as superior predictive platforms for testing of drugs but also of drug delivery systems [20]. …”

Section: Discussionmentioning

confidence: 99%

Photoinduced effects of m-tetrahydroxyphenylchlorin loaded lipid nanoemulsions on multicellular tumor spheroids

et al. 2016

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BackgroundPhotosensitizers are used in photodynamic therapy (PDT) to destruct tumor cells, however, their limited solubility and specificity hampers routine use, which may be overcome by encapsulation. Several promising novel nanoparticulate drug carriers including liposomes, polymeric nanoparticles, metallic nanoparticles and lipid nanocomposites have been developed. However, many of them contain components that would not meet safety standards of regulatory bodies and due to difficulties of the manufacturing processes, reproducibility and scale up procedures these drugs may eventually not reach the clinics. Recently, we have designed a novel lipid nanostructured carrier, namely Lipidots, consisting of nontoxic and FDA approved ingredients as promising vehicle for the approved photosensitizer m-tetrahydroxyphenylchlorin (mTHPC).ResultsIn this study we tested Lipidots of two different sizes (50 and 120 nm) and assessed their photodynamic potential in 3-dimensional multicellular cancer spheroids. Microscopically, the intracellular accumulation kinetics of mTHPC were retarded after encapsulation. However, after activation mTHPC entrapped into 50 nm particles destroyed cancer spheroids as efficiently as the free drug. Cell death and gene expression studies provide evidence that encapsulation may lead to different cell killing modes in PDT.ConclusionsSince ATP viability assays showed that the carriers were nontoxic and that encapsulation reduced dark toxicity of mTHPC we conclude that our 50 nm photosensitizer carriers may be beneficial for clinical PDT applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0221-x) contains supplementary material, which is available to authorized users.

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“…Also Sambale et al investigated the morphology of spheroids during their formation in the presence of NPs. 77 In that study, the administration of increasing noncytotoxic concentrations of TiO 2 NPs caused the formation of larger numbers of spheroids per well besides formation of smaller spheroids. 77 In contrast, after application of cytotoxic doses of ZnO NPs, the diameter of the spheroid was observed to increase due to lowered cell-cell interactions.…”

Section: Penetration Of Sio 2 Nps In 3d Liver Microtissuesmentioning

confidence: 86%

<p>Distribution of SiO<sub>2</sub> nanoparticles in 3D liver microtissues</p>

Fleddermann

Susewind²,

Peuschel

et al. 2019

IJN

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Introduction: Nanoparticles (NPs) are used in numerous products in technical fields and biomedicine; their potential adverse effects have to be considered in order to achieve safe applications. Besides their distribution in tissues, organs, and cellular localization, their impact and penetration during the process of tissue formation occurring in vivo during liver regeneration are critical steps for establishment of safe nanomaterials. Materials and methods: In this study, 3D cell culture of human hepatocarcinoma cells (HepG2) was used to generate cellular spheroids, serving as in vitro liver microtissues. In order to determine their differential distribution and penetration depth in HepG2 spheroids, SiO 2 NPs were applied either during or after spheroid formation. The NP penetration was comprehensively studied using confocal laser scanning microscopy and scanning electron microscopy. Results: Spheroids were exposed to 100 µg mL −1 SiO 2 NPs either at the beginning of spheroid formation, or during or after formation of spheroids. Microscopy analyses revealed that NP penetration into the spheroid is limited. During and after spheroid formation, SiO 2 NPs penetrated about 20 µm into the spheroids, corresponding to about three cell layers. In contrast, because of the addition of SiO 2 NPs simultaneously to cell seeding, NP agglomerates were located also in the spheroid center. Application of SiO 2 NPs during the process of spheroid formation had no impact on final spheroid size. Conclusion: Understanding the distribution of NPs in tissues is essential for biomedical applications. The obtained results indicate that NPs show only limited penetration into already formed tissue, which is probably caused by the alteration of the tissue structure and cell packing density during the process of spheroid formation.

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Three dimensional spheroid cell culture for nanoparticle safety testing

Cited by 78 publications

References 33 publications

Evaluation of CdTe/CdS/ZnS core/shell/shell quantum dot toxicity on three-dimensional spheroid cultures

Evaluation of CdTe/CdS/ZnS core/shell/shell quantum dot toxicity on three-dimensional spheroid cultures

Photoinduced effects of m-tetrahydroxyphenylchlorin loaded lipid nanoemulsions on multicellular tumor spheroids

<p>Distribution of SiO<sub>2</sub> nanoparticles in 3D liver microtissues</p>

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Three dimensional spheroid cell culture for nanoparticle safety testing

Cited by 78 publications

References 33 publications

Evaluation of CdTe/CdS/ZnS core/shell/shell quantum dot toxicity on three-dimensional spheroid cultures

Evaluation of CdTe/CdS/ZnS core/shell/shell quantum dot toxicity on three-dimensional spheroid cultures

Photoinduced effects of m-tetrahydroxyphenylchlorin loaded lipid nanoemulsions on multicellular tumor spheroids

<p>Distribution of SiO<sub>2</sub>&nbsp;nanoparticles&nbsp;in 3D liver microtissues</p>

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<p>Distribution of SiO<sub>2</sub> nanoparticles in 3D liver microtissues</p>