Minimizing protein corona formation around nanoparticles by using stealth polymer is a current strategy to limit non-specific cellular uptake and to increase blood circulation time. In addition, the antifouling property is a prerequisite for specific targeting and drug delivery. PEG coating is most commonly used for this purpose but zwitterionic surface chemistry appears as an interesting alternative. The wide range of possible variations of zwitterionic materials is clearly an advantage compared to PEG but in return, the impact of the molecular design on protein-adsorption properties must be optimized. Here, we present some results about interactions between polyzwitterionic coated quantum dots and albumin or whole serum. Sulfobetaine, phosphorylcholine and carboxybetaine based polymers have been synthesized by RAFT. A terminal vinylimidazole block was added at the end of the polyzwitterion to ensure anchoring at the quantum dots surface. Hard protein corona formation was quantified after ultracentrifugation by fluorescamine assay. Fluorescence Correlation Spectroscopy (FCS) was used to characterize dynamic interactions between proteins and QDs directly. We found that sulfobetaine based polymer is able to totally prevent hard and soft corona formation with BSA and proteins of serum around nanoparticles making this polymer ideal for antifouling applications. The phosphorylcholine and carboxybetaine ligands are less efficient and induce formation of few aggregates in serum. Intracellular trajectories of individual QD injected into Hela cells have been analyzed. The high diffusion coefficient (D60ms ~0.8 um2s-1) and the purely Brownian motion point to the remarkable cytoplasmic inertness of these zwitterionic coated nanoparticles. This enables in turn efficient intracellur targeting in live cells. Finally, we will discuss the impact of the modification of globally neutral polyzwitterions by the addition of some negatively or positively charged monomers on protein adsorption and intracellular diffusion.

Antifouling zwitterionic quantum dot surface chemistry: Impact on intracellular diffusion

2019 Spring National Meeting

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