The grafting of linear polyethylene glycol (PEG) is a common strategy in ascribing the stealth effect to nanostucture against protein adsorption for biomedical applications. However, PEG is not biodegradable and may still evoke side effects<i> in vivo</i> that compromises the circulation and efficacy of PEGylated drugs or nanocarrier. Recently, we demonstrated the synthesis of brushed phosphorylcholine (PC) as biomimetic alternative to linear PEG for the grafting of superparamagnetic iron oxide nanoparticles (IONP). Compared to brushed PEG (bPEG), brushed PC (bPC) rendered even better suspendability, stability, biocompatibility and cellular distribution. To further examine the structures of bPEG and bPC and directly test their antifouling properties against proteins, discrete molecular dynamics (DMD) simulations were performed. We found that brushed polymers were more rigid than the linear PEG while bPEG and bPC ligands displayed distinct globular and cylindrical morphologies. Grafting either bPEG or bPC onto IONPs led to different characteristics of the grafting layer, namely ligand coverage, height, and conformational strains both laterally and vertically. Upon mixing both bPEG and bPC onto the same IONP surface while maintaining the same grafting density, a conformational relaxation of the bPEG was observed in DMD simulations, as corroborated by fluorescence quenching of Cy5 attached to bPEGs in the experiment. Both bPEG- and bPC-grafted NPs displayed antifouling against human serum albumin (HSA), with an increased grafting density giving rise to enhanced protein avoidance. Our results suggest that, with a stronger repulsion to HSA and the capability to a higher grafting density due to its cylindrical shape, bPC is more advantage than both linear and brushed PEG for grafting NPs with minimal protein binding. These new structural and energetic insights offer a general guidance for NP synthesis and anti-fouling applications employing branched polymers.

Brushed polymers as promising grafting agents against protein binding

253rd National Meeting (2017)

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