Photodynamic therapy-induced anticandidal effects via reactive oxygen species generation from bisdemethoxycurcumin...

Antimicrobial photodynamic therapy (aPDT) is a promising non-pharmacological approach for managing biofilm-associated fungal infections. In this study, we investigated the antifungal efficacy of a double-agent aPDT system combining bisdemethoxycurcumin (BDMC) as a photosensitizer and potassium iodide (KI) as a photodynamic enhancer against Candida albicans biofilms, with particular emphasis on the underlying reactive oxygen species (ROS)-mediated mechanisms. Mature C. albicans biofilms were treated with BDMC alone (20, 40, and 80 µM), KI alone (100 mM), or their combination, followed by dental blue LED irradiation (430 ± 10 nm LED, 200 mW/cm², 0-100 J/cm²). Biofilm viability was assessed, and ROS generation quantified using fluorescence-based assays and electron paramagnetic resonance spectroscopy. The contribution of specific ROS to antifungal activity was evaluated through Spearman correlation analyses. The combined BDMC-KI aPDT system produced significantly greater biofilm inactivation than single-agent treatments. Enhanced antifungal activity was strongly associated with increased singlet oxygen (¹O₂) generation, while hydroxyl radicals contributed to a lesser extent. These findings support a double-mode photodynamic mechanism in which BDMC-derived ROS are chemically amplified by iodide, yielding longer-lived reactive iodine species and oxidative intermediates that enhance biofilm disruption. Overall, this study demonstrates that KI functions as an effective photodynamic potentiator rather than a photosensitizer, significantly augmenting BDMC-mediated aPDT against C. albicans biofilms. The mechanistic insights gained here support the further development of double-agent photodynamic strategies for the management of drug-resistant fungal biofilm infections. Clinical relevance: Bisdemethoxycurcumin+potassium iodide act as a photosensitizer in PDT to inhibit Candida albicans biofilms.