Nanoparticle (NP) aggregation can lead to prolonged retention in tissues or embolism. Successful use in biomedicine thus requires the capability to make NPs with limited aggregative potential. Rational design is presently a challenge due to incomplete knowledge of their interactions in biofluids. Recently, ultrasmall gold NPs passivated with endogenous surfactants have shown promise for use <i>in vivo</i>. Computer simulations are here conducted to identify the forces underlying aggregation (or lack thereof) of these NPs in a cell culture. Electrostatic interactions are insufficient to induce association, but the van der Waals forces exerted by cations, anions, and net-neutral polar species can promote the formation of stable dimers by eliciting an imbalance of forces at the NP/NP interface. The entropic effects of depletion are negligible, but the combined effect of depletion and macromolecular crowding at physiological concentrations can stabilize aggregates containing just a few NPs. Interparticle interactions are controlled by modest changes in both the structure and dynamic of the interfacial liquid. The molecular origin of these effects and their dependence on NP size are described. The liquid is shown to be highly structured, with large and long-lived hydrogen-bonded water clusters developing often at the NP/liquid interface; their potential role as transient, long-range proton wires connecting and enveloping NPs are discussed. These results provide the basis for a parsimonious theory of ultrasmall NPs in complex fluids.

Computational study of interfacial forces driving aggregation of ultrasmall nanoparticles in biofluids

255th National Meeting (2018)

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