Upconverting nanoparticles (UCNPs) are a unique class of luminescent nanomaterials capable of converting near-infrared (NIR) excitation energy into visible and ultraviolet emission. This property is particularly beneficial for biomedical imaging, as UCNPs can be excited by NIR light within a biological imaging window (750-1300 nm), where tissue absorption and scattering are minimal. This enables deeper tissue penetration than conventional fluorophores that are excited with visible or ultraviolet light [1]. However, a significant challenge in biomedical applications of nanoparticles is their limited accumulation and penetration in certain organs or tumors. To achieve prolonged circulation in the bloodstream and reduce rapid clearance by the mononuclear phagocyte system, surface functionalization strategies such as polyethylene glycol (PEG) coating are commonly used. PEGylation enhances the nanoparticles’ hydrophilicity, reduces protein adsorption, and minimizes immune recognition, thereby improving their biocompatibility and systemic retention for in vivo imaging and therapeutic applications [2]. In this study, core-shell UCNPs with the chemical composition NaGdF\(_{4}\):Yb\(^{3+}\),Er\(^{3+}\)@NaGdF\(_{4}\):Yb\(^{3+}\),Nd\(^{3+}\), were synthesized according to the previously described procedure [3]. The surfaces of these nanoparticles were functionalized using custom-designed brush-type copolymers p(DMAm-co-OEG\(_{X}\)MA). These copolymers incorporate oligoethylene glycol chains of varying lengths (x = 5, 9, 19) on the UCNP surface.
This study aimed to investigate how the length of PEG substituents affects the cellular uptake of UCNPs. Emission intensity measurements indicated that these modified UCNPs demonstrate long-term stability in aqueous and cell culture media. The intracellular accumulation of UCNPs using laser scanning confocal microscopy and spectrometry was used to evaluate their applicability on different cancer cell lines derived from distinct localizations (breast and prostate cancer) and skin-derived mesenchymal stem cells (S-MSCs). The study revealed that all modified UCNPs exhibited similar uptake behavior in cell monolayers. The accumulation studies were also conducted on cellular spheroids to bring the study closer to the in vivo environment. The results indicated that UCNPs accumulate on the surface layers of the spheroids regardless of the length of the PEG substituent. Additional biocompatibility tests confirmed that UCNPs are biocompatible and exhibited no toxicity within the investigated cells. All these findings concluded that functionalized UCNPs are promising biocompatible agents for bioimaging. This project has received funding from the Research Council of Lithuania (LMTLT), agreement No [S-MIP-23-5].