May the target be with you: polysaccharide-coated upconverting nanoparticles for macrophage targeting

Abstract

Upconversion nanoparticles (UCNPs) based on β-NaYF₄ doped with Yb³⁺ and Er³⁺ are promising candidates for multimodal bioimaging and theranostic applications, owing to their unique optical properties and favourable safety profile. However, their limited stability under physiological conditions and lack of effective cellular targeting continue to restrict their clinical translation. Here, we report a surface functionalisation strategy using hydroxybisphosphonate-modified polysaccharides-specifically mannan and inulin-to improve both colloidal stability and biological performance of UCNPs. Mannan with grafted hydroxybisphosphonate anchor groups formed a robust coating that prevented aggregation in phosphate-buffered and serum-containing media, while preserving upconversion luminescence. Crucially, the mannan-functionalised surface enabled selective interaction with mannose receptor (MR)-expressing macrophages (J774A.1), facilitating efficient cellular uptake as demonstrated by confocal microscopy and receptor inhibition assays. In vitro studies confirmed the high biocompatibility of mannan-coated UCNPs across a broad concentration range (0.5-10 μg mL^-1), with no significant cytotoxicity or oxidative stress observed. This streamlined and effective surface modification approach yields a stable, receptor-targeted nanoplatform with strong potential for future in vivo diagnostic and therapeutic applications involving immune cells.