Self-luminescing BRET-FRET near infrared dots for in vivo lymph node mapping and tumor imaging

Strong autofluorescence from living tissues, and the scattering and absorption of short-wavelength light in living tissues, significantly reduce sensitivity of in vivo fluorescence imaging. These issues can tackled by using imaging probes that emit in the near-infrared (NIR) wavelength range. Here we describe self-luminescing NIR-emitting nanoparticles employing an energy transfer relay that integrates bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), enabling in vivo NIR imaging without external light excitation. Nanoparticles were 30-40 nm in diameter, contained no toxic metals, exhibited long circulation time and high serum stability, and produced strong NIR emission. Using these nanoparticles, we successfully imaged lymphatic networks and vasculature of xenografted tumors in living mice. The self-luminescing feature provided excellent tumor-to-background ratio (>100) for imaging very small tumors (2-3 mm in diameter). Our results demonstrate that these new nanoparticles are well suited to in vivo imaging applications such as lymph node mapping and cancer imaging.