Magnetic molding of tumor spheroids: emerging model for cancer screening

Three-dimensional tissue culture, and particularly spheroid models, have recently been recognized as highly relevant in drug screening, toxicity assessment and tissue engineering due to their superior complexity and heterogeneity akin to the in vivo microenvironment. However, limitations in size control, shape reproducibility and long maturation times hinder their full applicability. Here, we report a spheroid formation technique based on the magnetic aggregation of cells with internalized magnetic nanoparticles. The method yields magnetic spheroids with high sphericity and allows fine-tuning the final spheroid diameter. Moreover, cohesive spheroids can be obtained in less than 24 h. We show the proof of concept of the method using the CT26 murine colon carcinoma cell line and how different cell proliferation and invasion potentials can be attained by varying the spheroid size. Additionally, we show how the spheroid maturation impacts cell invasion and doxorubicin penetrability, highlighting the importance of this parameter in drug screening and therapeutic applications. Finally, we demonstrate the capability of the method to allow the measurement of the surface tension of spheroids, a relevant output parameter in the context of cancer cell invasion and metastasis. The method can accommodate other cell lines able to be magnetically labeled, as we demonstrate using the U-87 MG human glioblastoma cell line, and shows promise in the therapeutic screening at early time points of tissue formation, as well as in studies of drug and nanoparticle tumor penetration.