Boosting often overlooked long wavelength emissions of rare-earth nanoparticles for NIR-II fluorescence imaging of orthotopic glioblastoma

Rare-earth nanoparticles (RE NPs) with narrow long wavelength emissions have been recently investigated for their potential application for fluorescence imaging in the second near-infrared window (NIR-II). Previously these RE NPs have a very limited application in the diagnosis and treatment of deep-seated tumors such as brain tumors, due to their weak fluorescence in the range of 1300-1700 nm. Herein, we report a significant enhancement of more than 10 times regular emission of NaNdF4 nanoparticles at 1340 nm wavelength by coating them with an inert layer of NaLuF4, followed by sensitizing with a near-infrared dye (IR-808). We deliver these highly bright nanoparticles into the brain by using focused ultrasound to temporarily open the blood-brain barrier (BBB), and then detect the orthotopic glioblastoma by fluorescence imaging at 1340 nm. The images obtained from long wavelength fluorescence (i.e. 1340 nm) exhibited better resolution and contrast compared to the short wavelength fluorescence (i.e. 1060 nm). Our study not only provides insights for enhancing often overlooked emissions of rare-earth nanoparticles for NIR-II fluorescence imaging of deep-seated tumors, but also demonstrates great potential of focused ultrasound based technology in delivering nanotheranostic agents.