Optically Robust and Biocompatible Mechanosensitive Upconverting Nanoparticles

Abstract

Upconverting nanoparticles (UCNPs) are promising tools for background-free imaging and sensing. However, their usefulness for <i>in vivo</i> applications depends on their biocompatibility, which we define by their optical performance in biological environments and their toxicity in living organisms. For UCNPs with a ratiometric color response to mechanical stress, consistent emission intensity and color are desired for the particles under nonmechanical stimuli. Here, we test the biocompatibility and mechanosensitivity of α-NaYF₄:Yb,Er@NaLuF₄ nanoparticles. First, we ligand-strip these particles to render them dispersible in aqueous media. Then, we characterize their mechanosensitivity (∼30% in the red-to-green spectral ratio per GPa), which is nearly 3-fold greater than those coated in oleic acid. We next design a suite of <i>ex vivo</i> and <i>in vivo</i> tests to investigate their structural and optical properties under several biorelevant conditions: over time in various buffers types, as a function of pH, and <i>in vivo</i> along the digestive tract of <i>Caenorhabditis elegans</i> worms. Finally, to ensure that the particles do not perturb biological function in <i>C. elegans</i>, we assess the chronic toxicity of nanoparticle ingestion using a reproductive brood assay. In these ways, we determine that mechanosensitive UCNPs are biocompatible, i.e., optically robust and nontoxic, for use as <i>in vivo</i> sensors to study animal digestion.