ZnPc(Lys)5-mediated photodynamic inactivation and reduction of Candida albicans biofilm-associated cells in vitro and in vivo

Introduction Candida-associated stomatitis is a common oral mucosal condition, particularly among denture wearers, and is closely associated with persistent Candida albicans biofilms on denture surfaces. ZnPc(Lys) 5 is an amphiphilic phthalocyanine–peptide nanomaterial that has previously been shown to form nanoscale supramolecular assemblies in aqueous environments. This study evaluated the efficacy of ZnPc(Lys) 5 -mediated antimicrobial photodynamic therapy (aPDT) in reducing denture-associated Candida biofilms and alleviating associated mucosal inflammation. Methods Candida albicans suspensions were cultured in vitro , and biofilms were formed on polymethyl methacrylate (PMMA), a common denture base material. The antifungal effects of different concentrations of ZnPc(Lys) 5 combined with aPDT were assessed against both planktonic Candida and biofilms. Biofilm structural changes were observed by scanning electron microscopy, and the effects on PMMA physical properties (microhardness [HV] and surface roughness [Ra]) were analyzed. Additionally, a mouse model of Candida-associated stomatitis was used to evaluate the in vivo anti-inflammatory and antifungal efficacy of ZnPc(Lys) 5 -aPDT following repeated applications (three treatments over 5 days). Results ZnPc(Lys) 5 -mediated aPDT exerted a significant concentration-dependent fungicidal effect on planktonic C. albicans , with a minimum effective concentration (MEC) of 25 μM and no observed dark toxicity. Against mature biofilms, the 50 μM aPDT treatment achieved a reduction of approximately 96% in recoverable viable biofilm-associated cells (P < 0.0001), which was comparable to the efficacy of the commercial cleanser Polident (P > 0.05). Scanning electron microscopy confirmed significant disruption of biofilm architecture, while no significant alterations in PMMA microhardness or surface roughness were observed (P > 0.05). In vivo , repeated applications of ZnPc(Lys) 5 -aPDT significantly reduced epithelial hyperplasia and inflammatory infiltration, demonstrating therapeutic efficacy comparable to nystatin. Conclusion ZnPc(Lys) 5 -aPDT demonstrated significant antifungal activity in vitro and in vivo without compromising PMMA integrity. These findings support ZnPc(Lys) 5 as a promising photosensitizer for denture-surface biofilm control and mucosal inflammation mitigation, warranting further investigation under extended or multi-session clinical protocols.