Intraparticle Energy Level Alignment of Semiconducting Polymer Nanoparticles to Amplify Chemiluminescence for Ultrasensitive in Vivo Imaging of Reactive Oxygen Species

Detection of reactive oxygen species (ROS), a hallmark of many pathological processes, is imperative to understanding, detection and treatment of many life-threatening diseases. However, methods capable of real-time in situ imaging of ROS in living animals are still very limited. We herein report the development and optimization of chemiluminescent semiconducting polymer nanoparticles (SPNs) for ultrasensitive in vivo imaging of hydrogen peroxide (H₂O₂). The chemiluminescence is amplified by adjusting the energy levels between the luminescence reporter and the chemiluminescence substrate to facilitate intermolecular electron transfer in the process of H₂O₂-activated luminescence. The optimized SPN can emit chemiluminescence with the quantum yield up to 2.30 × 10^-2 einsteins/mol and detect H₂O₂ down to 5 nM, which substantially outperforms the previous probes. Further doping of this SPN with a naphthalocyanine dye creates intraparticle chemiluminescence resonance energy transfer (CRET), leading to the near-infrared (NIR) luminescence responding to H₂O₂. By virtue of high brightness and ideal NIR optical window, SPN-NIR permits ultrasensitive imaging of H₂O₂ in the mouse models of peritonitis and neuroinflammation with the minute administration quantity. Thus, this study not only provides a category of optical probes that eliminates the need of external light excitation for imaging of H₂O₂, but also reveals the underlying principle to enhance the brightness of chemiluminescence systems.