An impediment to random walk: trehalose microenvironment drives preferential endocytic uptake of plasmonic nanoparticles

Developing effective theranostic nanoplex platforms for personalized disease treatment necessitates an understanding of and the ability to control live cell–nanoparticle interactions. However, aggregation of nanoparticles on the cell surface and their subsequent internalization is sparsely understood and adversely impact cellular recognition and viability. Here we report a facile method of precisely modulating the aggregation and uptake for silver nanoparticles without altering their surface geometry or functionalization. Exploiting the stabilization properties of trehalose, our approach enables uptake of nanoparticles while reducing aggregation on cell surface and maintaining cell viability. Electron microscopy reveals the larger utilization of endosomal structures in the trehalose-rich environment compared to the nanoparticles' “free” cytosolic diffusion patterns in the control group. Additionally, in the presence of trehalose, plasmon-enhanced Raman spectroscopy confirms the preservation of the protein structure in the vicinity of the nanoparticles reinforcing the promise of the proposed route for label-free, multiplexed intracellular monitoring.