Self-Immolative Polymer-Based Chemiluminescent Nanoparticles for Long-Term In Vivo Imaging of Reactive Oxygen Species

Chemiluminescence (CL) provides a favorable technique for reactive oxygen species (ROS) imaging with high specificity and negligible background noise; however, the short duration limits its clinical applications in disease diagnosis. In this work, we serendipitously discover that the nanoparticles (NPs), consisting of a self-immolative polymer (SIP) and hydrophobic dyes, induce sustained CL, which is available for long-term in vivo ROS imaging. In response to ROS, SIP undergoes stepwise head-to-tail degradation and sustainably transfers energy to the dyes to emit CL. With this unique domino-like degradation mechanism, the SIP-based CL-NPs generate highly efficient ROS-selective CL signals for at least 6 h, superior to those provided by CL-NPs containing small-molecule CL donors. When intravenously administered, the SIP-based CL-NPs clearly and precisely illuminate the ROS-abundant regions in four typical inflammatory disease models for hours. These findings suggest that SIP-based CL-NPs are potential contrast agents for in vivo ROS imaging and disease diagnosis.