Functionalization of rare-earth nanoparticles with hybrid silica-lipid shells for T-cell labeling

Lanthanide-doped nanophosphors are an emergent class of optical materials very attractive for biological imaging as they offer deep tissue penetration lengths, high contrast and minimal autofluorescence. An exciting and relatively unexplored application of these nanoparticles is the ability to label and track immune cell populations non-invasively. However, biological application of these nanoparticles is often limited by the challenges in surface functionalization of these nanocrystals. In this study, we engineer methods to functionalize NaYF₄ (Yb, Er) nanoparticles with hybrid silica-lipid shells and demonstrate successful and stable labelling of immune cells (T-lymphocytes) for the formation of near-infrared fluorescent immune cells. We use super-resolution microscopy to characterize cell labeling at nanoscale resolution and show individual nanoparticles bound or internalized to T-cells. These surface medication methods are modular and customizable to enable targeting to a variety of cell types, with the potential for broad applications in a variety of disease phenomena such as non-invasive visualization of cell-based therapies.