Optically Robust and Biocompatible Mechanosensitive Upconverting Nanoparticles

Abstract

Upconverting nanoparticles (UCNPs) are promising tools for background-free imaging and sensing. However, their usefulness for in vivo 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-NaYF 4 :Yb,Er@NaLuF 4 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 ex vivo and in vivo tests to investigate their structural and optical properties under several biorelevant conditions: over time in various buffers types, as a function of pH, and in vivo along the digestive tract of Caenorhabditis elegans worms. Finally, to ensure that the particles do not perturb biological function in C. elegans , 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 in vivo sensors to study animal digestion.

Integration of luminal pressure and signalling in tissue self-organization

“…This device has been shown to detect changes in cytoplasmic pressure when the cells are subjected to osmotic shock (Gómez-Martínez et al, 2013). Similarly, metallic nanoparticles have been developed to measure forces in the nano-to micro-Newton range (Lay et al, 2017(Lay et al, , 2019Shen et al, 2008). These particles change their crystal structures in response to high pressure, leading to a shift in fluorescence emission intensity that can be calibrated to infer the pressure.…”

<p>Up-Conversion Luminescent Nanoparticles for Molecular Imaging, Cancer Diagnosis and Treatment</p>

“…To date, toxicity assessment of UCNPs have been carried out in Caenorhabditis elegans ( C. elegans ), zebrafish, and mice. 101–104 The results suggested that delivery of UCNPs by feeding showed less toxicity in both C. elegans and zebrafish. The most reported delivery of UCNPs into living mice were focused on intravenous injection, and UCNPs could be accumulated in reticuloendothelial systems.…”

Applications and regulatory of nanotechnology‐based innovative in vitro diagnostics

“…NMs are promising candidates as signal generators for IVDs and provide more options for conventional IVDs, benefiting from their unique size‐dependent physical and chemical properties, such as optical, 4 thermodynamic, 5 and magnetic performances 6 . In comparison with fluorescence probes, quantum dots (QDs), 7–10 up‐conversion nanoparticles (UCNPs), 11–14 and long‐persistent NMs 15–17 exhibited the superior features of high fluorescence brightness, good stability, and low background noise.…”