Surface Coverage-Regulated Cellular Interaction of Ultrasmall Luminescent Gold Nanoparticles

Investigations for accurately controlling the interaction between functional nanoparticles (NPs) and living cells set a long-thought benefit in nanomedicine and disease diagnostics. Here, we reveal a surface coverage-dependent cellular interaction by comparing the membrane binding and uptake of three ultrasmall luminescent gold NPs (AuNPs) with different surface coverages. Lower surface coverage leads to fast cellular interaction and strong membrane binding but low cellular uptake, whereas high surface coverage induces slow cellular interaction and low membrane binding but major cellular uptake. The slight number increase of cell-penetrating peptide on the surface of AuNPs shows improved cellular interaction dynamics and internalization through direct cellular membrane penetration. Furthermore, the different intrinsic emissions resulted from the surface coverage variation, especially the pH-responsive dual emissions, make the AuNPs powerful optical probes for subcellular imaging and tracking. The findings advance the fundamental understanding of the cellular interaction mechanisms of ultrasmall AuNPs and provide a feasible strategy for the design of functional NPs with tunable cellular interaction by surface regulation.