Bisphosphonate‐Modified Polymer‐Coated <scp> NaYF ₄ :Yb,Er,Pr </scp> Upconverting Nanoparticles for Cell Imaging: Synthesis, Physicochemical Characterization and Biosafety

Upconverting nanoparticles (UCNPs) have attracted much attention in nanomedicine due to their ability to upconvert photons. However, their adverse effects hinder the biomedical applications. In this paper, bisphosphonate-modified poly(isobutylene-alt-maleic acid)-graft-poly(N,N-dimethylacrylamide)-coated NaYF₄:Yb,Er,Pr UCNPs (UCNP@PIMAPDMA) nanoparticles were designed, which exhibited luminescence emission simultaneously in the visible and NIR-II regions. The developed UCNPs were characterized by a range of physicochemical methods, including transmission electron and energy dispersive microscopy (TEM and EDAX), dynamic light scattering (DLS), X-ray diffraction analysis (XRD), spectrofluorometry, X-ray photoelectron spectroscopy (XPS), and so forth. The UCNP@PIMAPDMA nanoparticles were also evaluated in cell cultures and experimental animals. The particles showed good biocompatibility with cultured human embryonic kidney HEK293 cells commonly used in toxicological studies. Neat UCNPs were cytotoxic towards these cells, which was confirmed by measuring their viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Blood serum proteins adhered to the surface of UCNP@PIMAPDMA particles, forming a protein corona that may contribute to particle biosafety. After intravenous injection of these particles into laboratory mice, there were no statistically significant changes in body mass of the treated animals. Also, no big adverse effects on blood cell profile, enzymatic and metabolic markers of hepatotoxicity and nephrotoxicity were observed. Finally, the application potential of UCNP@PIMAPDMA nanoparticles was confirmed by successfully imaging the cytoplasm of rat mesenchymal stem cells and rat C6 glioblastoma cells using laser scanning confocal microscopy.