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

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 (approximate to 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 1O2 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. A new approach is developed to enhance the afterglow luminescence of existing substrates by using a functional protein (bovine serum albumin) coating. Its application in surgical navigation and image-guided cancer surgery is demonstrated with tumor-mimicking phantoms and ex vivo porcine models. image