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BMC Proceedings

Open Access

Multicellular tumor spheroids in microcapsules as a novel 3D in vitro model in tumor biology

  • Elena Markvicheva1Email author,
  • Daria Zaytseva-Zotova1,
  • Roman Akasov1,
  • Sergey Burov2,
  • Isabelle Chevalot3 and
  • Annie Marc3
BMC Proceedings20137(Suppl 6):P116

https://doi.org/10.1186/1753-6561-7-S6-P116

Published: 4 December 2013

Background

Advantages of microencapsulation as a 3D growth system are chemically and spatially defined 3D network of extracellular matrix components, cell-to-cell and cell-to-matrix interactions governing differentiation, proliferation and cell function in vivo. The study is aimed at i) optimization of techniques for preparing microcapsules; ii) generation of multicellular tumor spheroids (MTS) by culturing tumor cells in the microcapsules; iii) study of anticancer treatment effects for both photodynamic therapy (PDT) and anti-cancer drug screening. The model allows to estimate drug doses or parameters for PDT in vitro before carrying out preclinical tests, and thereby to reduce a number and costs of experiments with animals commonly used.

Materials and methods

To form MTS, tumor cell lines (mouse melanoma cells M3, human breast adenocarcinoma cells MCF-7, mouse myeloma Sp2/0 cells, human CCRF-CEM and CEM/Cl cell lines, HeLa) were encapsulated in polyelectrolyte microcapsules (200-600 μm), and cultivated for 3-4 weeks [1]. Microcapsules were fabricated from alginate (polyanion) and various polycations, namely natural polymers (modified chitosan, DEAE-dextran etc) and novel smart co-polymers (e.g. chitosan-graft-polyvinyl alcohol copolymers) synthesized by a Solid-State Reactive Blending technique [2]. The copolymers were characterized by FTIR, GPC and elemental analysis.

Results

MTS based MCF-7 cells were prepared and used to study effects of PDT. To study the effect of irradiation parameters on cell viability, 2 photosensitizers (PS), namely photosense and chlorine e6 were used. Phototoxicity of PS depended on PS concentration and light energy density in both monolayer culture (MLC) and MTS. Study of cell morphology in MLC and MTS before and after PDT revealed that light energy density increase within the range of 30-70 J/cm2 resulted in cell apoptosis. However, cell survival in MTS was much higher than this in the MLC. MTS were also used to test some antitumor therapeutics (methotrexate, doxorubicin and their derivatives). An enhanced cell resistance in MTS compared to MLC both for normal and Dox-resistant cells (MCF-7, MCF-7/DXR, respectively) were observed. MTS were also proposed to evaluate cytotoxicity not only of novel therapeutics but also nanosized drug delivery systems (liposomes, micelles, nanoparticles and nanoemulsions).

Declarations

Acknowledgements

The authors are greatful to Dr. T. Akopova (Moscow) for synthesis of chitosan-graft-polyvinyl alcohol copolymers used in this study. The authors also thank CNRS and Russian foundation for basic research for support of the research (PICS-Russia project N° 5598 - 2010-2012).

Authors’ Affiliations

(1)
Shemyakin-Ovchinnikov Inst Bioorg Chem Rus Acad Sci
(2)
Institute of Macromolecular Compounds Rus Acad Sci
(3)
CNRS, Laboratoire Réactions et Génie des Procédés, UMR 7274, Université de Lorraine

References

  1. Zaytseva-Zotova D, Marc A, Chevalot I, Markvicheva E: Biocompatible Smart Microcapsules Based on Chitosan-Poly(Vinyl Alcohol) Copolymers for Cultivation of Animal Cells. Adv Eng Mater. 2011, 13: B493-B503.View ArticleGoogle Scholar
  2. Akopova TA, Moguilevskaia EL, Ozerin AN, Zelenetskii AN, Vladimirov LV, Zhorin VA: Proc Int Conf Mechanochemical Synthesis and Sintering. 2004, Novosibirsk, 199-Google Scholar

Copyright

© Markvicheva et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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