Dye-Sensitized Upconversion Nanoparticles with Enhanced Aqueous Luminescence for Neuronal Imaging

The combination of organic dyes as photosensitizers with inorganic upconversion nanoparticles (UCNPs) has significantly enhanced upconversion luminescence when excited by near-infrared (NIR) light. Additionally, by employing surface functionalization techniques, a high signal-to-noise ratio can be achieved, resulting in exceptional resolution for bio-imaging. The objective of our project is to develop a heptamethylcyanine derivative (IR61-BF) for dye-sensitized UCNPs, enhancing their luminescence efficiency in aqueous solutions. This is done by introducing a difluorobenzene group into the cyanine structure. Rare earth-doped UCNPs with a core-shell structure, NaYF₄:YbTm@NaYF₄:YbNd, are synthesized using a high-temperature decomposition method. In this structure, the Nd³⁺ ions function as efficient sensitizers by absorbing 808 nm NIR light. To further enhance upconversion efficiency, the molecular structure of the NIR dye IR61 was optimized. By integrating a difluorinated phenyl group into the cyanine backbone, we significantly increased the fluorescence quantum yield of the dye and enhanced the dye sensitization effect of the UCNPs. Subsequently, the UCNPs are coated with an amphiphilic ligand, DSPE-PEG, and IR61-BF is incorporated into the hydrophobic region between the UCNPs, achieve a remarkable 167.1-fold enhancement in UCL in the aqueous phase. Their biocompatibility for neuronal imaging is evaluated using NSC34, Neuro2a, and C6 glioma cells, while its potential for retrograde intra-neuronal delivery is confirmed by using a microfluidic model of cortical neurons. We demonstrated that the newly synthesized heptamethine cyanine derivative IR61-BF shows exceptional sensitization of UCNPs by incorporating a difluorobenzene group, particularly in aqueous solutions.