Near‐Infrared Afterglow Luminescence Amplification via Albumin Complexation of Semiconducting Polymer Nanoparticles for Surgical Navigation in Ex Vivo Porcine Models

Abstract Afterglow imaging, leveraging persistent luminescence following light cessation, has emerged as a promising modality for surgical interventions. However, the scarcity of efficient near‐infrared (NIR) responsive afterglow materials, along with their inherently low brightness and lack of cyclic modulation in afterglow emission, has impeded their widespread adoption. Addressing these challenges requires a strategic repurposing of afterglow materials that improve on such limitations. Here, an afterglow probe, composed of bovine serum albumin (BSA) coated with an afterglow material, a semiconducting polymer dye (SP1), called BSA@SP1 demonstrating a substantial amplification of the afterglow luminescence (≈3‐fold) compared to polymer‐lipid coated PFODBT (DSPE‐PEG@SP1) under same experimental conditions is developed. This enhancement is believed to be attributed to the electron‐rich matrix provided by BSA that immobilizes SP1 and enhances the generation of 1 O 2 radicals, which improves the afterglow luminescence brightness. Through molecular docking, physicochemical characterization, and optical assessments, BSA@SP1's superior afterglow properties, cyclic afterglow behavior, long‐term colloidal stability, and biocompatibility are highlighted. Furthermore, superior tissue permeation profiling of afterglow signals of BSA@SP1's compared to fluorescence signals using ex vivo tumor‐mimicking phantoms and various porcine tissue types (skin, muscle, and fat) is demonstrated. Expanding on this, to showcase BSA@SP1's potential in image‐guided surgeries, tumor‐mimicking phantoms within porcine lungs and conducted direct comparisons between fluorescence and afterglow‐guided interventions to illustrate the latter's superiority is implanted. Overall, the study introduces a promising strategy for enhancing current afterglow materials through protein complexation, resulting in both ultrahigh signal‐to‐background ratios and cyclic afterglow signals.