Specific, Surface-Driven, and High-Affinity Interactions of Fluorescent Hyaluronan with PEGylated Nanomaterials

Hybrid nanomaterials are a subject of extensive research in nanomedicine, and their clinical application is reasonably envisaged in the near future. However, the fate of nanomaterials in biological environments poses serious limitations to their application; therefore, schemes to monitor them and gain control on their toxicity could be of great help for the development of the field. Here, we propose a probe for PEGylated nanosurfaces based on hyaluronic acid (HA) functionalized with rhodamine B (RB). We show that the high-affinity interaction of this fluorogenic hyaluronan (HA-RB) with nanoparticles exposing PEGylated surfaces results in their sensing, labeling for super-resolution imaging, and synergistic cellular internalization. HA-RB forms nanogels that interact with high affinity—down to the picomolar range—with silica nanoparticles, selectively when their surface is covered by a soft and amphiphilic layer. This surface-driven interaction triggers the enhancement of the luminescence intensity of the ...