Strategic Insights into Engineering Parameters Affecting Cell Type-Specific Uptake of DNA-Based Nanomaterials

Abstract

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.

Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!

“…Furthermore, in light of a recent study showing that the efficiency of the cellular uptake of DNA nanostructures may be modulated by the chemical properties of the attached fluorophore and its position [ 65 ], we cannot exclude that the uptake of the unlabeled aptamers may differ from the fluorescein-labeled ones. On the other hand, our data, based on the use of the same fluorophore, pointed out that, among the three studied aptamers, MS3 is the most efficiently adsorbed one by SH-SY5Y cells.…”

Integration of functional peptides into nucleic acid-based nanostructures

“…3b). 47 This stabilizing approach enabled systematic studies into the impact of the DNA origami shape and mass 96 as well as different surface properties 95 on their uptake into different types of cells. Furthermore, Anastassacos and colleagues were able to enhance the protective effect of the PEG-oligolysine coatings by chemically crosslinking the polymers with glutaraldehyde, increasing the survival time of the underlying DNA structures against enzymatic degradation by an additional factor of 250.…”

DNA Nanotechnology‐Empowered Live Cell Measurements

“…Koga et al. also examined the parameters of the cell entry of the DNA nanostructures in different cell types, [ 72 ] and discovered that the cell type was complex and responded differently to DNA nanostructures. In addition, small changes in the charge, fluorescent dye, and coating on the surface of the DNA nanostructure were found to induce cell‐dependent uptake differences.…”

“…[71] In this assay, the researchers found that the compactness and aspect ratio of the DNA nanostructure were important to cellular uptake, while the cell entry of the DNA nanostructures was more cell-type-dependent. Koga et al also examined the parameters of the cell entry of the DNA nanostructures in different cell types, [72] and discovered that the cell type was complex and responded differently to DNA nanostructures. In addition, small changes in the charge, fluorescent dye, and coating on the surface of the DNA nanostructure were found to induce cell-dependent uptake differences.…”