%0 Journal Article %T Modulated Cell Internalization Behavior of Icosahedral DNA Framework with Programmable Surface Modification. %A Huang K %A Yang Q %A Bao M %A Wang S %A Zhao L %A Shi Q %A Yang Y %J J Am Chem Soc %V 146 %N 31 %D 2024 Aug 7 %M 39038211 %F 16.383 %R 10.1021/jacs.4c04106 %X Surface modification could enhance the cell internalization efficiency of nanovehicles for targeted gene or drug delivery. However, the influence of surface modification parameters, including recognition manners, valences, and patterns, is often clouded, especially for the endocytosis of DNA nanostructures in customized shapes. Focusing on an icosahedral DNA framework, we systematically programmed three distinct types of ligands with diverse valence and spatial distribution on their outer surface to study the internalization efficiency, endocytic pathways, and postinternalization fate. The comparison in different aspects of parameters deepens our understanding of the intricate relationship between surface modification and cell entry behavior, offering insights crucial for designing and optimizing DNA framework nanostructures for potent cell-targeted purposes.