Mechanical forces influence many biological processes, including cell differentiation, muscle contraction, and disease. However, few sensors have the nanoscopic size or dynamic range to measure forces in vivo. Lanthanide-doped nanoparticles are an emerging class of optical probes due to their biocompatible features, including sharp emission peaks, high signal-to-noise, and photostability. In recent work, we found that cubic-phase (α) upconverting nanoparticles (UCNPs) are at least 2x more mechanosensitive than hexagonal-phase (β) UCNPs. Unfortunately, the centrosymmetric crystal field environment, which allows for high mechanosensitivity in cubic-phase UCNPs, also contributes to their low quantum yield (QY). In this work, we engineer brighter mechanosensitive core-shell UCNPs for biological applications. Sub-25 nm α-NaYF4:Yb,Er cores are shelled with an optically-inert surface passivation layer of ~4.5 nm thickness. Using different shell materials, including NaGdF4, NaYF4 and NaLuF4, we study how compressive to tensile strain, as confirmed by X-ray diffraction, influences the nanoparticles' imaging and sensing properties. All core-shell nanoparticles exhibit enhanced UCQY, up to 0.14% at 150 W/cm2, which rivals the efficiency of unshelled hexagonal-phase nanoparticles. Using a diamond anvil cell, we perform in situ spectroscopy to characterize mechanosensitivity. Comparing shell types, the compressive NaGdF4 results in the largest color response, from yellow-green to orange emission or quantitatively, Ir/Ig = 12.2 ± 1.2% per GPa. All color responses consistent over three pressure cycles and stable for hours under near infrared illumination. For bio-compatibility, we modify the nanoparticle surface (e.g. ligand-strip, polymer-wrap) and further, monitor how pH and temperature influence optical properties. Finally, we demonstrate the first in vivo application of these UCNPs in the C. elegans pharynx. The worms are incubated with UCNPs overnight for feeding and then loaded in a microfluidic device for spectra collection. Based on ratiometric differences in emission peaks, we find that forces exerted in the grinder are nearly an order of magnitude higher than those exerted at the pharyngeal-intestinal valve.

Mechanosensitive upconverting nanoparticles for visualizing mechanical forces in vivo

256th National Meeting (2018)

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