Near-Infrared Light-Triggered NO/Photodynamic Synergistic Therapy with Antibacterial and Biofilm-Eliminated Effects for Difficult-to-Treat Rhinosinusitis

Chronic rhinosinusitis (CRS) is a complex condition that affects an individual's well-being and quality of life. While there are current treatment options like medication and surgery, an increasing number of patients experience difficult-to-treat rhinosinusitis (DTRS). To address this challenge, a highly efficient intelligent nanoplatform (ALCe6 NPs) has been developed, which is formed by loading chlorin e6 (Ce6) onto nanoliposomes composed of cholesterol modified with l-arginine and soybean phospholipids. Under near-infrared (NIR) light stimulation, Ce6 is efficiently activated to generate reactive oxygen species (ROS), leading to the controlled release of nitric oxide (NO). This synergistic effect of ROS generated from photodynamic therapy (PDT) and NO release enables the dispersion of bacterial biofilms and the effective eradication of drug-resistant bacteria. Genome analysis of the combined antibacterial action of ALCe6 NPs reveals changes in genes related to cellular metabolism, transcription processes, and bacterial resistance. To evaluate the therapeutic efficacy of ALCe6 NPs in treating DTRS caused by methicillin-resistant Staphylococcus aureus (MRSA) infection, a rat model is constructed to monitor the treatment process and assess the outcomes. With its significant advantages, ALCe6 NPs show promising potential as a biomedical tool to combat drug-resistant bacterial infections in vivo, offering hope for managing DTRS and improving patient outcomes.