Recently, the role of complex biomacromolecular interactions with cytosolic components was shown to play a critical role in the release of oligonucleotides upon internalisation . Indeed, a broad range of macromolecules, including cytosolic RNA and proteins associated with RNA/DNA binding and translation were found to rapidly associate at the surface of polymer brush-based gene delivery vectors. Such processes were proposed to not only impact on the release of oligonucleotide, through competitive binding, but also impact on the recruitment of translational components, potentially altering their activity. In addition, the macromolecular architecture of polymer brushes was found to impact their capacity to bind oligos, using a combination of surface plasmon resonance and fluorescence microscopy assays, and in turn, their transfection and knock down efficiency . Therefore, the oligonucleotide binding capacity and architecture of resulting complexes is proposed to play a significant role in the long term maintenance of resulting vectors stability, retention of nucleic acid materials and ultimately their timely delivery upon internalisation. However, resolving the precise architecture of these complexes remains challenging. Recently, neutron reflectometry was applied to gain such insight and showed that RNA oligonucleotides are able to infiltrate deep into the structure of PDMAEMA and PMETAC brushes, potentially underpinning the high capacity of these coatings for the capture of these macromolecules, as well as their protection from early escape or degradation, and timely release .