Uptake and intracellular trafficking of nanoparticles upon exposure to the cells are tightly regulated through their interactions with cellular organelles, which ultimately determines the distribution and fate in the cells. However, current understanding on the physicochemical characteristics of a nanoparticle and its interactions with a surrounding cell is still unclear. As a result, it remains questions how to optimally synthesize and chemically modify nanomaterials for biological applications. Here, we report the role of surface chemistry in mediating serum protein adsorption to the nanoparticles and their cellular uptake. To suppress nonspecific serum protein adsorption efficiently, secondary packaging of the surface chemistry is suggested, and we proved that the short chain of antifouling polyethylene glycol is helpful to block forming protein corona. The grafting density of polyethylene glycol determines the variations in serum protein adsorption, followed by cellular uptake mechanism and quantity of the nanoparticles. We found the chain length of the polyethylene glycol has to be less than that of the ligand linker in order to not interfere with the binding of the targeting moiety to its target receptor, although the polyethylene glycol has been known to facilitate the reduction of nonspecific binding of proteins to the nanoparticles. The results suggest an optimized surface configuration on the nanoparticles for enhanced intracellular uptake and trafficking to the target organelles. Essentially, effective control of the serum protein and nanoparticle interactions is important to understand the detailed mechanisms at the nano-bio interface. Furthermore, the study suggest poly(ethyl ethylene phosphate) as an alternative of conventional polyethylene glycol. Our study will open a way on rational design of nanoparticle and surface chemistry for targeted delivery of nanoparticles carrying chemo- and gene-therapeutics.

Secondary packaging of nanoparticles for enhanced intracellular trafficking

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.