Optical imaging of combined fluorescent cellular spheroids and study of their growth under the influence of chemotherapy
Sogomonyan A. S. 1,2, Kotelnikova P. A. 1, Demin D. E. 3, Mirkasymov A. B. 1,4, Deyev S. M. 1,4,5, Zvyagin A. V. 1,4,6
1Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia
2Institute of Engineering Physics for Biomedicine, National Research Nuclear University (MEPhI), Moscow, Russia
3Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
4Institute of Molecular Theranostics, Sechenov First Moscow State Medical University, Moscow, Russia
5Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
6MQ Photonics Centre, Macquarie University, Sydney, Australia
Email: annasogomonyan2012@mail.ru, polina.kotelnikova27@gmail.com, denisdeminbio@gmail.com, mirkasymov@phystech.edu, biomem@mail.ru, andrei.zvyagin@mq.edu.au

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The development of new drugs for cancer treatment requires a deeper understanding of carcinogenesis mechanisms and their more accurate reproduction. The creation of 3D cell models was an important step in the study of tumor stroma and the reconstruction of a relevant cancer model. Using 3D-printing and micromolding, we obtained polymer molds for the rapid formation of cellular spheroids, their long-term incubation and microscopy. The molds were used to create spheroids from cancer, stromal cells, and their combinations. In order to distinguish tumor and stromal cells during co-cultivation, they were transduced with genes of fluorescent proteins in different regions of the visible spectrum. Fluorescence microscopy allowed not only to observe the dynamics of spheroid growth, but also to evaluate separately the sensitivity of cancer and stromal cells to cytostatic therapy. The developed form simplifies the reconstruction of a relevant 3D cancer model and testing of cytotoxic drugs. The results obtained demonstrate the importance of optical methods in studying the antitumor efficiency of drugs. Keywords: 3D-printing, multicellular tumor spheroids, fluorescent microscopy, cisplatin, chemotherapy.
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