Mingdong Huang

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.

Background: Compared to the lymphodepleting chemotherapy and radiotherapy, photodynamic therapy (PDT) is an oncotherapeutic modality inherently stimulating immune responses by inducing immunogenic cell death (ICD). However, the immunosuppressive tumor microenvironment (TME) frequently attenuates PDT-elicited immune responses, limiting its efficacy in eradicating distant and metastatic tumor cells. Methods: To maximize the immunotherapeutic efficacy of PDT, we developed a photodynamic immunotherapeutic liposomal nanoplatform (PDIT-liposome) integrating components targeting sequential stages of the antitumor immune response: 1) a phthalocyanine photosensitizer to induce ICD, 2) a factor Xa inhibitor (rivaroxaban) to promote T-cell priming, 3) and a program death-ligand 1 inhibitor to augment cytotoxic T lymphocyte (CTL) attack. To enable light-controlled drug release at tumor sites, the liposome was constructed with reactive oxygen species-sensitive phospholipids in response to the PDT effect. Results: PDIT-liposomes were characterized via multiple physicochemical and optical evaluations. Comprehensive in vitro and in vivo investigations confirmed that PDIT-liposomes significantly enhanced antitumor efficacy compared to monotherapies and dual combinations. In a subcutaneous implantation tumor model, PDIT-liposome achieved a 91.7% antitumor rate compared to 21.83% (P-liposome), 46.78% (PD-liposome), and 51.08% (PR-liposome) (p < 0.001). Mechanistic analysis revealed enhanced dendritic cell maturation (8-fold increase in CD11c + cells) and T-cell priming (2.3-fold increase in CD8 + T cells) in tumor-draining lymph nodes (TDLNs), and CTL-mediated cytotoxicity (5.4-fold increase in CD107a + activated CTLs) in TME. Notably, PDIT therapy induced long-term immunological memory, which suppressed 90.68% tumor reoccurrence and metastasis. Conclusion: This study presents a strategy to amplify PDT-elicited immunotherapeutic efficacy by synergizing agents targeting distinct stages of the immune response. It also theoretically validates the synergy of PDT, anticoagulation therapy, and immune checkpoint inhibition in cancer treatment.