3D Tumor Models—Nanomedicine in the Third Dimension

Abstract

Over the past decades, impressive breakthroughs have been made in cancer therapies. Namely, the development of multifunctional nanomaterials with enhanced efficacy and reduced side effects has marked a significant step forward in cancer research. However, the promising results observed in preclinical studies show low translatability into the clinic, due to a lack of adequate preclinical models that faithfully mimic the complex tumor microenvironment. Cancer research and drug screening are traditionally performed on 2D in vitro monolayer cultures and subsequently validated in in vivo animal models. Nonetheless, oversimplistic 2D cultures do not accurately represent the physiological 3D tumor architecture and lack adequate cell–cell and cell–matrix interactions. Meanwhile, animal models fail to properly replicate the human tumor microenvironment and are associated with high variability, costs, and ethical limitations. The 3D cell culture systems are a growing area of research to bridge the gap between traditional 2D drug-screening platforms/animal models, and the human body. These tridimensional cancer models better recapitulate in vivo tumor features and have demonstrated more clinically relevant therapeutic responses in comparison with 2D and animal models. This chapter provides a comprehensive overview of the available 3D cancer cell models to date, including scaffold-free and scaffold-based techniques for tumor spheroid formation, a description of patient-derived tumor organoids/tumoroids, and 3D microfluidic-based strategies. In doing so, we pinpoint each model's main advantages and disadvantages and highlight their relevance as preclinical models for nanomedicine.