Highly doped upconversion nanoparticles for in vivo applications under mild excitation power

One of the major challenges in using upconversion nanoparticles (UCNPs) is to improve their brightness. This is particularly true for in vivo studies, as the low power excitation is required to prevent the potential photo toxicity to live cells and tissues. Here, we report that the typical NaYF₄:Yb_0.2,Er_0.02 nanoparticles can be highly doped, and the formula of NaYF₄:Yb_0.8,Er_0.06 can gain orders of magnitude more brightness, which is applicable to a range of mild 980 nm excitation power densities, from 0.005 W/cm² to 0.5 W/cm². Our results reveal that the concentration of Yb³⁺ sensitizer ions plays an essential role, while increasing the doping concentration of Er³⁺ activator ions to 6 mol % only has incremental effect. We further demonstrated a type of bright UCNPs 12 nm in total diameter for in vivo tumor imaging at a power density as low as 0.0027 W/cm², bringing down the excitation power requirement by 42 times. This work redefines the doping concentrations to fight for the issue of concentration quenching, so that ultrasmall and bright nanoparticles can be used to further improve the performance of upconversion nanotechnology in photodynamic therapy, light-triggered drug release, optogenetics, and night vision enhancement.