Improving the Subcutaneous Mouse Tumor Model by Effective Manipulation of Magnetic Nanoparticles-Treated Implanted Cancer Cells
Murine tumor models have played a fundamental role in the development of novel therapeutic interventions and are currently widely used in translational research. Specifically, strategies that aim at reducing inter-animal variability of tumor size in transplantable mouse tumor models are of particular importance. In our approach, we used magnetic nanoparticles to label and manipulate colon cancer cells for the improvement of the standard syngeneic subcutaneous mouse tumor model. Following subcutaneous injection on the scruff of the neck, magnetically-tagged implanted cancer cells were manipulated by applying an external magnetic field towards localized tumor formation. Our data provide evidence that this approach can facilitate the formation of localized tumors of similar shape, reducing thereby the tumor size’s variability. For validating the proof-of-principle, a low-dose of 5-FU was administered in small animal groups as a representative anticancer therapy. Under these experimental conditions, the 5-FU-induced tumor growth inhibition was statistically significant only after the implementation of the proposed method. The presented approach is a promising strategy for studying accurately therapeutic interventions in subcutaneous experimental solid tumor models allowing for the detection of statistically significant differences between smaller experimental groups.
KeywordsMagnetic nanoparticles Subcutaneous/transplantable mouse tumor model BALB/c mice CT26 cells Preclinical screening
Dulbecco’s modified Eagle medium
Inductively coupled plasma optical emission spectrometry
Fluorescently-labeled magnetic nanoparticles
Part of the work was implemented by utilizing the facilities of the ‘OPENSCREEN-GR’ supported by the National Roadmap for Research Infrastructures under the National Strategy for Research, Technological Development, and Innovation (2014–2020) by the General Secretariat for Research and Technology (GSRT), Ministry of Education and Religious Affairs, Hellenic Republic.
Conflict of interest
Authors have no conflicts of interest to declare.
- 9.Friedrich, R. P., C. Janko, M. Poettler, P. Tripal, J. Zaloga, I. Cicha, S. Dürr, J. Nowak, S. Odenbach, I. Slabu, M. Liebl, L. Trahms, M. Stapf, I. Hilger, S. Lyer, and C. Alexiou. Flow cytometry for intracellular SPION quantification: specificity and sensitivity in comparison with spectroscopic methods. Int. J. Nanomed. 10:4185, 2015.CrossRefGoogle Scholar
- 22.Schleich, N., P. Sibret, P. Danhier, B. Ucakar, S. Laurent, R. N. Muller, C. Jérôme, B. Gallez, V. Préat, and F. Danhier. Dual anticancer drug/superparamagnetic iron oxide-loaded PLGA-based nanoparticles for cancer therapy and magnetic resonance imaging. Int. J. Pharm. 447:94–101, 2013.CrossRefGoogle Scholar
- 23.Seeliger, H., M. Guba, G. E. Koehl, A. Doenecke, M. Steinbauer, C. J. Bruns, C. Wagner, E. Frank, K. W. Jauch, and E. K. Geissler. Blockage of 2-deoxy-D-ribose-induced angiogenesis with rapamycin counteracts a thymidine phosphorylase-based escape mechanism available for colon cancer under 5-fluorouracil therapy. Clin. Cancer Res. 10:1843–1852, 2004.CrossRefGoogle Scholar
- 26.Spyridopoulou, K., A. Tiptiri-Kourpeti, E. Lampri, E. Fitsiou, S. Vasileiadis, M. Vamvakias, H. Bardouki, A. Goussia, V. Malamou-Mitsi, M. I. Panayiotidis, A. Galanis, A. Pappa, and K. Chlichlia. Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models. Sci. Rep. 7:3782, 2017.CrossRefGoogle Scholar
- 27.Suggitt, M., and M. C. Bibby. 50 years of preclinical anticancer drug screening : empirical to target-driven approaches. Clin. Cancer Res. 11:971–981, 2005.Google Scholar