Tight binding of optically innocent bisphosphonate ligands to robust Tb3+-doped HfO2 nanocrystal surfaces

Lanthanide (Ln3+)-doped nanocrystals feature photostable, long-lived emission, making them attractive probes for in vitro and in vivo imaging. Their translation, however, hinges on a surface chemistry that confers colloidal stability under physiological conditions without compromising their photophysical properties. Here, we benchmark three classes of PEGylated anchoring groups—nitrocatecholates, phosphonates and bisphosphonates—on core and core/shell Tb3+-doped HfO2 nanocrystals. Nitrodopamine-based ligands quench Tb3+ luminescence in water on both core and core/shell particles, whereas phosphonic and bisphosphonic acids are optically innocent and leave the emission intact. Nuclear magnetic resonance (NMR) and dynamic light scattering (DLS) reveal that only the bisphosphonates remain tightly bound and keep the nanocrystals dispersed across a wide pH range and in phosphate-buffered saline (PBS). Nanocrystals capped with PEGylated bisphosphonate (bisPA−PEG250) retain their luminescence after prolonged incubation in PBS, with no detectable Hf or Tb leaching. Thus, PEGylated bisphosphonates emerge as robust, non-perturbing ligands for Ln3+-doped HfO2 and as a practical entry point to biomedical application, since Tb3+-doped HfO2 can be used as probes in bio-imaging of leukemia cells.