Functional PEG–PAMAM-Tetraphosphonate Capped NaLnF₄ Nanoparticles and their Colloidal Stability in Phosphate Buffer

Developing surface coatings for NaLnF₄ nanoparticles (NPs) that provide long-term stability in solutions containing competitive ions such as phosphate remains challenging. An amine-functional polyamidoamine tetraphosphonate (NH₂-PAMAM-4P) as a multidentate ligand for these NPs has been synthesized and characterized as a ligand for the surface of NaGdF₄ and NaTbF₄ nanoparticles. A two-step ligand exchange protocol was developed for introduction of the NH₂-PAMAM-4P ligand on oleate-capped NaLnF₄ NPs. The NPs were first treated with methoxy-poly­(ethylene glycol)-monophosphoric acid (<i>M</i>_n = 750) in tetrahydrofuran. The mPEG750-OPO₃-capped NPs were stable colloidal solutions in water, where they could be ligand-exchanged with NH₂-PAMAM-4P. The surface amine groups on the NPs were available for derivatization to attach methoxy-PEG (<i>M</i>_n = 2000) and biotin-terminated PEG (<i>M</i>_n = 2000) chains. The surface coverage of ligands on the NPs was examined by thermal gravimetric analysis, and by a HABA analysis for biotin-containing NPs. Colloidal stability of the NPs was examined by dynamic light scattering. NaGdF₄ and NaTbF₄ NPs capped with mPEG2000–PAMAM-4P showed colloidal stability in DI water and in phosphate buffer (10 mM, pH 7.4). A direct comparison with NaTbF₄ NPs capped with a mPEG2000-lysine-based tetradentate ligand that we reported previously (Langmuir 2012, 28, 12861−12870) showed that both ligands provided long-term stability in phosphate buffer, but that the lysine-based ligand provided better stability in phosphate-buffered saline