One-pot synthesis of water-soluble and carboxyl-functionalized β-NaYF4:Yb,Er(Tm) upconversion nanocrystals and their application for bioimaging

Poor water-solubility and biocompatibility are the biggest obstacles for the bioapplications of upconversion nanophosphors (UCNPs). In this work, a facile solvothermal approach was developed for the one-pot synthesis of monodisperse and water-soluble β-NaYF4 UCNPs by employing poly(acrylic acid, sodium salt) (PAAs) as the capping reagent. The as-prepared UCNPs were thoroughly characterized and a possible reaction mechanism is proposed, which indicates that PAAs plays a crucial role for the shape and phase evolution of the NaYF4 UCNPs. More importantly, each multidentate PAA can tightly bind to the UCNPs surface through multiple –COO− groups, while an abundance of uncoordinated carboxyl groups on the polymer chain extend into the solution, making the UCNPs highly water-soluble. The presence of free carboxyl groups on the surfaces also facilitates the conjugation of the UCNPs with various biomolecules, which paves the way for further bio-applications. As a proof-of-concept model, transferrin was covalently linked to β-NaYF4:Yb,Er to form the transferrin–UCNPs conjugates, which have been successfully applied to the high-contrast fluorescent imaging and detection of HeLa cells. Possessing the advantages of good biocompatibility and inherent high upconversion efficiency, our directly synthesized β-NaYF4 UCNPs exhibit great potential as excellent bio-probes for in vitro or in vivo imaging, detection and diagnosis.