DNA-based nanomaterials
are gaining popularity as uniform and programmable
bioengineering tools as a result of recent solutions to their weak
stability under biological conditions. The DNA nanotechnology platform
uniquely allows decoupling of engineering parameters to comprehensively
study the effect of each upon cellular encounter. We here present
a systematic analysis of the effect of surface parameters of DNA-based
nanoparticles on uptake in three different cell models: tumor cells,
macrophages, and dendritic cells. The influence of surface charge,
stabilizing coating, fluorophore types, functionalization technique,
and particle concentration employed is found to cause significant
differences in material uptake among these cell types. We therefore
provide new insights into the large variance in cell type-specific
uptake, highlighting the necessity of proper engineering and careful
assay development when DNA-based materials are used as tools in bioengineering
and as future nanotherapeutic agents.