Surface Plasmon-Enhanced NIR-II Fluorescence in a Multilayer Nanoprobe for Through-Skull Mouse Brain Imaging

Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds great potential for the accurate visualization of deeply located biological structures in vivo. However, the weak fluorescence of current NIR-II fluorophores remains a long-standing challenge for the ever-growing imaging demand. Here, we describe a surface plasmon-enhanced NIR-II fluorescence strategy by incorporating silica-coated gold nanorods (GNRs) and polymer dots (Pdots) into a multilayer nanostructure. Precise manipulation of the silica spacing layer thickness signifies an optimum distance of 8.6 nm, where an enhancement factor of up to 6.4 is achieved in the NIR-II imaging window. The surface plasmon enhancement approach is successfully extended to several types of Pdots fluorophores with NIR-II emission. We finally perform outer-layer encapsulation and PEGylation for the multilayer probes and demonstrate surface plasmon-enhanced NIR-II fluorescence for mouse brain imaging through the skull, which exhibits a refined signal-to-background ratio and penetration depth as compared to the clinically approved ICG dye.