Liver Tumor Spheroid Reconstitution for Testing Mitochondrial Targeted Magnetic Hyperthermia Treatment

Mitochondria-targeting nanotherapy receives great attention these days for its capacity in disrupting mitochondria function and inducing tumor cell apoptosis through external magnetic and optical stimulations. However, the effect is significantly diminished when applied to animal models. The key factors include environmental complexity in vivo and intrinsic protective features of tumor tissues. To address these obstacles and reduce expenses on drug screening, we herein introduce a methodology for producing millimeter-sized spheroids with structural and functional characteristics of tumor tissues in vivo. The necessity of spheroid as a liver tumor model is demonstrated by comparing the effect of TPP-SPIONs (triphenylphosphonium cation-superparamagnetic iron oxide nanoparticles) on monolayer-cultured HepG2 cells and spheroids. Our study reveals that large-scale spheroid, in contrast to monolayer cells, reflects more in vivo tumor characters and is less responsive to TPP-SPIONs during magnetic hyperthermia treatment.