Enhanced Near-Infrared-Excitable Organic Afterglow Nanoparticles for Deep-Tissue Multimodal Imaging via Singlet Oxygen-Mediated Energy Transfer

Afterglow imaging offers exceptional signal-to-background ratios (SBRs) by circumventing real-time excitation and autofluorescence, yet conventional systems rely on visible-light excitation, limiting tissue penetration and signal intensity. Here, we report near-infrared-excitable organic afterglow nanoparticles (NOANPs) that leverage singlet oxygen (¹O₂)-mediated energy transfer to achieve prolonged, high-intensity emission with minimal photobleaching. The nanoparticles integrate a near-infrared-photoactive sensitizer (NAM-0), which generates abundant ¹O₂ under 808-nm laser excitation, and a triplenet-anthracene derivative (TD) as the afterglow substrate, which converts ¹O₂ into sustained luminescence. Co-encapsulation via one-step nanocoprecipitation ensures proximity between NAM-0 and TD, enabling efficient energy transfer and yielding exceptional afterglow brightness (>10⁹ photons/s) at ultralow concentrations (10 μg/ml). NOANPs enable deep-tissue imaging (up to 3.0 cm ex vivo) by synergizing the superior penetration of near-infrared light with organic afterglow chemistry. The nanoparticles uniquely support three imaging modes: fluorescence, white light-activated afterglow, and near-infrared-triggered afterglow, which were validated in orthotopic murine models of pancreatic cancer and glioma. By synergizing near-infrared excitation with organic afterglow chemistry, this work overcomes longstanding limitations in penetration depth of excitation light, offering a versatile tool for precision imaging.