Ultra-stable near-infrared Tm3+-doped upconversion nanoparticles for in vivo wide-field two-photon angiography with a low excitation intensity

Abstract

Two-photon luminescence with near-infrared (NIR) excitation of upconversion nanoparticles (NPs) is of great importance in biological imaging due to deep penetration in high-scattering tissues, low auto-luminescence and good sectioning ability. Unfortunately, common two-photon luminescence is in visible band with an extremely high exciation power density, which limits its application. Here, we synthesized NaYF4:Yb/Tm@NaYF4 upconversion NPs with strong two-photon NIR emission and a low excitation power density. Furthermore, NaYF4:Yb/Tm@NaYF4@SiO2@OTMS@F127 NPs with high chemical stability were obtained by a modified multilayer coating method which was applied to upconversion NPs for the first time. In addition, it is shown that the as-prepared hydrophillic upconversion NPs have great biocompatibility and kept stable for 6 hours during in vivo whole-body imaging. The vessels with two-photon luminescence were clear even under an excitation power density as low as 25mW/cm2. Vivid visualizations of capillaries and vessels in a mouse brain were also obtained with low background and high contrast. Because of cheaper instruments and safer power density, the NIR two-photon luminescence of NaYF4:Yb/Tm@NaYF4 upconversion NPs could promote wider application of two-photon technology. The modified multilayer coating method could be widely used for upconversion NPs to increase the stable time of the in vivo circulation. Our work possesses a great potential for deep imaging and imaging-guided treatment in the future.

Keywords

• Ultra-stable upconversion nanoparticles
• two-photon luminescence
• in vivo brain angiography
• low excitation power density