Surface Plasmon‐Enhanced Short‐Wave Infrared Fluorescence for Detecting Sub‐Millimeter‐Sized Tumors

Abstract Short‐wave infrared (SWIR, 900–1700 nm) enables in vivo imaging with high spatiotemporal resolution and penetration depth due to the reduced tissue autofluorescence and decreased photon scattering at long wavelengths. Although small organic SWIR dye molecules have excellent biocompatibility, they have been rarely exploited as compared to their inorganic counterparts, mainly due to their low quantum yield. To increase their brightness, in this work, the SWIR dye molecules are placed in close proximity to gold nanorods (AuNRs) for surface plasmon‐enhanced emission. The fluorescence enhancement is optimized by controlling the dye‐to‐AuNR number ratio and up to ≈45‐fold enhancement factor is achieved. In addition, the results indicate that the highest dye‐to‐AuNR number ratio gives the highest emission intensity per weight and this is used for synthesizing SWIR imaging probes using layer‐by‐layer (LbL) technique with polymer coating protection. Then, the SWIR imaging probes are applied for in vivo imaging of ovarian cancer and the surface coating effect on intratumor distribution of the imaging probes is investigated in two orthotopic ovarian cancer models. Lastly, it is demonstrated that the plasmon‐enhanced SWIR imaging probe has great potential for fluorescence imaging‐guided surgery by showing its capability to detect sub‐millimeter‐sized tumors.