Surface Topography of Polyethylene Glycol Shell Nanoparticles Formed from Bottlebrush Block Copolymers Controls Interactions with Proteins and Cells.

Although poly(ethylene glycol) (PEG) is commonly used in nanoparticle design, the impact of surface topography on nanoparticle performance in biomedical applications has received little attention, despite showing significant promise in the study of inorganic nanoparticles. Control of the surface topography of polymeric nanoparticles is a formidable challenge due to the limited conformational control of linear polymers that form the nanoparticle surface. In this work, we establish a straightforward method to precisely tailor the surface topography of PEGylated polymeric nanoparticles based on tuning the architecture of shape-persistent amphiphilic bottlebrush block copolymer (BBCP) building blocks. We demonstrate that nanoparticle formation and surface topography can be controlled by systematically changing the structural parameters of BBCP architecture. Furthermore, we reveal that the surface topography of PEGylated nanoparticles significantly affects their performance. In particular, the adsorption of a model protein and the uptake into HeLa cells were closely correlated to surface roughness and BBCP terminal PEG block brush width. Overall, our work elucidates the importance of surface topography in nanoparticle research as well as provides an approach to improve the performance of PEGylated nanoparticles.