Design strategy of surface decoration for efficient delivery of nanoparticles by computer simulation

Understanding the role of surface decoration of nanoparticles in protein adsorption and cellular uptake is of great importance in biomedicine. Here, by using dissipative particle dynamics simulations, we take two typical coating polymers (i.e., hydrophilic and zwitterionic polymers) as an example, and systematically investigate their effect on cellular delivery of hydrophobic and charged nanoparticles (in the presence of serum protein). Our results show that though two types of polymers are charge-neutral and can both reduce the protein adsorption, there exist some differences between their ability of protein resistance, especially in the case of positively charged nanoparticles. Besides, it is found that the coating polymers may also greatly decrease the cellular uptake efficiency of nanoparticles. Nevertheless, and importantly, since the zwitterionic polymers may become positively charged under low pH environments, the nanoparticle can attach onto cell membrane more firmly than that coated with hydrophilic polymers, which can further enhance the active targeting of nanoparticles. Finally, we also provide the design maps for surface decoration to achieve efficient cellular delivery. These results can help better understand how to keep the balance between protein resistance and cell targeting, which may give some useful guidelines on optimal design of future nanomaterials in drug delivery.