In this context, the present study demonstrates clear differences in the adsorption profiles of different nucleic acid materials at the surface of PDMAEMA, one of the most broadly applied cationic polymers in precision therapeutic design. SPR data indicate a strong impact of the size of nucleic acid macromolecules interacting with brushes, but also, more surprisingly their type, with RNA capture occurring at significantly higher densities than DNA molecules. Comparison with adsorption with PMETAC indicates that such effective packing may be regulated by differences in hydrogen bonding, although such interactions remain yet to be formally evidenced. In addition, although higher molecular weight nucleic acid molecules adsorbed to lower levels at the surface of PDMAEMA and PMETAC brushes, their association constants were particularly high. This presumably stems from the entropic drive associated with polyelectrolyte-polyelectrolyte complex formation , expected to increase with the size of macromolecules. This observation also has a broader impact on the dissociation of the molecules, as competitive binding processes resulting in the displacement of nucleic acid during delivery, and their release upon internalisation will be impacted by the strength of these interactions, whether in the context of polymer brushes or other cationic delivery systems.