Controlling cellular packing and hypoxia in 3D tumor spheroids via DNA interactions

Tumor spheroids represent valuable in vitro models for studying cancer biology and evaluating therapeutic strategies. In this study, we investigated the impact of varying lengths of DNA-modified cell surfaces on spheroid formation, cellular adhesion molecule expression, and hypoxia levels within 4T1 mouse breast cancer spheroids. Through a series of experiments, we demonstrated that modifying cell surfaces with biotinylated DNA strands of different lengths facilitated spheroid formation without significantly altering the expression of fibronectin and e-cadherin, key cellular adhesion molecules. However, our findings revealed a notable influence of DNA length on hypoxia levels within the spheroids. As DNA length increased, hypoxia levels decreased, indicating enhanced intercellular spacing and porosity within the spheroid structure. These results contribute to a better understanding of how DNA modification of cell surfaces can modulate spheroid architecture and microenvironmental conditions. Such insights may have implications for developing therapeutic interventions targeting the tumor microenvironment to improve cancer treatment efficacy.