Dual-Functional Janus Nanoparticles for Synergistic Antibacterial-Antitumor Therapy in Oral Squamous Cell Carcinoma

Intratumor microorganisms can promote tumor initiation, development, metastasis, and therapeutic resistance in cancer. Previous studies have indicated that Porphyromonas gingivalis ( P. gingivalis ) accelerates the progression of oral squamous cell carcinoma (OSCC) through enhancing cancer cell stemness, promoting immune evasion, regulating cyclins, modulating inflammatory cytokine profiles, and remodeling the tumor microenvironment. In this study, a high detection rate of intratumor and intracellular P. gingivalis was observed in OSCC clinical patients, which suggested a potential association between P. gingivalis and OSCC pathogenesis. However, whether synergistic elimination of P. gingivalis during antitumor therapy can slow OSCC progression remains unknown. Thus, we engineered an anisotropic Janus nanoparticle-based drug delivery system utilizing Au nanoparticles (AuNPs) and porous silica carriers for tumor-targeted synergistic therapy. The Au–Ce6–SiO 2 -MTZ Janus nanoparticles (denoted as JCM) prevent primary tumor growth through the photosensitizer Chlorin e6 (Ce6)-mediated photodynamic therapy (PDT) and eliminate intracellular P. gingivalis via metronidazole (MTZ) simultaneously. Our results demonstrate that the Au–Ce6–SiO 2 -MTZ Janus NPs enhance targeted nanomedicine delivery to tumor sites and improve the relevant therapeutic outcomes of P. gingivalis -infected models by synergistic antitumor-antibacterial in vitro and in vivo . Overall, this study introduces an effective OSCC treatment using a Janus nanoplatform that integrates antibacterial and photodynamic functions. It successfully targets tumor-promoting P. gingivalis , enhancing antitumor efficacy compared to PDT alone, while ensuring good biocompatibility.