Ratiometric near-infrared fluorescence nanothermometry in the OTN-NIR (NIR II/III) biological window based on rare-earth doped β-NaYF4 nanoparticles

Abstract

A novel nanothermometer based on over-1000 nm (OTN) near-infrared (NIR) emission of rare-earth doped ceramic nanophosphors (RED-CNPs) was developed for temperature measurement in deep tissue. Hexagonal-phase β-NaYF₄ nanoparticles co-doped with Yb³⁺, Ho³⁺, and Er³⁺ (NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs) were synthesized and used as a nanothermometer. The NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs displayed two OTN-NIR emission peaks in the second (NIR-II) (at 1150 nm of Ho³⁺) and third (NIR-III) (at 1550 nm of Er³⁺) biological window regions under NIR (980 nm) excitation in the first (NIR-I) biological window region. Oleic acid (OA) capped NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs were dispersed in non-polar media, i.e., cyclohexane, and showed a temperature-dependent intensity ratio of the emission peaks of Ho³⁺ and Er³⁺ (I_Ho/I_Er). The temperature-dependent I_Ho/I_Er of the OA-NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs was also evident through imitation tissue. The surfaces of the NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs were modified with a poly(ethylene glycol) (PEG)-based block copolymer. The PEGylated NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs were dispersed in water and emitted strong NIR-II and III emissions under NIR-I excitation. The PEGylated NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs were injected into mice via the tail vein, and the OTN-NIR emissions of the PEGylated NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs from the mouse blood vessels were clearly observed using an OTN-NIR fluorescence in vivo imaging system. In a polar media, water, the I_Ho/I_Er of PEGylated NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs was inversely related to the temperature. In both non-polar and polar media, the I_Ho/I_Er values of the NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs were almost linearly dependent on the temperature. The obtained NaYF₄:Yb³⁺,Ho³⁺,Er³⁺ NPs are promising as a novel fluorescent nanothermometer for deep tissue.