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, we have developed an afterglow probe, composed of bovine serum albumin (BSA) coated with an afterglow material, a semiconducting polymer dye (PFODBT/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. 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 molecule docking, physicochemical characterization, and optical assessments, we highlight BSA@SP1s superior afterglow properties, cyclic afterglow behavior, long-term colloidal stability, and biocompatibility. Furthermore, we demonstrate superior tissue permeation profiling of afterglow signals of BSA@SP1s compared to fluorescence signals using ex vivo tumor-mimicking phantoms and various porcine tissue types (skin, muscle, and fat). Expanding on this, to showcase BSA@SP1s potential in image-guided surgeries, we implanted tumor-mimicking phantoms within porcine lungs and conducted direct comparisons between fluorescence and afterglow-guided interventions to illustrate the latters superiority. Overall, our 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.