Embedded multicellular spheroids as a biomimetic 3D cancer model for evaluating drug and drug-device combinations

Multicellular aggregates of cells, termed spheroids, are of interest for studying tumor behavior and for evaluating the response of pharmacologically active agents. Spheroids more faithfully reproduce the tumor macrostructure found in vivo compared to classical 2D monolayers. We present a method for embedding spheroids within collagen gels followed by quantitative and qualitative whole spheroid and single cell analyses enabling characterization over the length scales from molecular to macroscopic. Spheroid producing and embedding capabilities are demonstrated for U2OS and MDA-MB-231 cell lines, of osteosarcoma and breast adenocarcinoma origin, respectively. Finally, using the MDA-MB-231 tumor model, the chemotherapeutic response between paclitaxel delivery as a bolus dose, as practiced in the clinic, is compared to delivery within an expansile nanoparticle. The expansile nanoparticle delivery route provides a superior outcome and the results mirror those observed in a murine xenograft model. These findings highlight the synergistic beneficial results that may arise from the use of a drug delivery system, and the need to evaluate both drug candidates and delivery systems in the research and preclinical screening phases of a new cancer therapy development program.