Work

Biomimetic nanotherapy for P. gingivalis-infected oral squamous cell carcinoma: Photothermal therapy and immunoactivation via precise intracellular bacterial elimination

Year: 2025

Type: article

Abstract: Porphyromonas gingivalis ( P. gingivalis ) infection in oral squamous cell carcinoma (OSCC) undermines patient responses to standard therapies by driving chemoresistance, tumor progression, and immune suppression. Mounting research evidence—including our staining of clinical OSCC biopsies—confirms intratumoral P. gingivalis colonization and CXCL2 overexpression as risk factors for poor prognosis. Therefore, precisely eliminating tumor-promoting microorganisms and alleviating immune suppression are crucial for improving the treatment efficacy. Inspired by validated observations, we have developed a unique clinically oriented nanoparticle platform (MC-MM@MPDA) that integrated precise intracellular antibiotic delivery, photothermal tumor ablation, photothermal bactericidal and immune activation. Despite growing interest in OSCC photothermal ablation, this platform is the first to utilize the dual anti-tumor and antibacterial functions of photothermal therapy aiming to achieve targeted therapy tailored to P. gingivalis -infected OSCC. Minocycline (MC) was loaded into mesoporous polydopamine (MPDA) nanoparticles and encapsulated with macrophage membranes, enabling selective homing to infected tumor sites and efficient uptake by cancer cells. Subsequently, the nanoplatform utilized photothermal effects to ablate tumor tissue, eliminate intracellular bacteria and induce immunogenic cell death (ICD). pH-triggered antibiotic release eradicated residual bacteria and unleashed bacterial tumor associated antigens. Alongside damage-associated molecular patterns (DAMPs) generated by ICD, these signals reprogrammed the immunosuppressive microenvironment and established a synergistic antitumor network. In P. gingivalis infected OSCC xenograft models, this platform dramatically suppressed tumor growth, cleared pathogen burden, and overcame bacteria-mediated therapy resistance. By leveraging membrane-mimetic targeting, and synergistic photothermal-immunotherapy, MC-MM@MPDA offered a scalable, biocompatible, and readily translatable strategy to address pathogen-driven barriers in OSCC therapy. • Intratumoral enrichment of P. gingivalis and consequent CXCL2 overexpression drive chemoresistance, foster an immunosuppressive microenvironment and poor prognosis in OSCC, underscoring the need for precise microbial elimination. • A novel clinical-oriented nanoplatform (MC-MM@MPDA) ingeniously integrates the dual antitumor and antibacterial functions of photothermal effect, precisely intracellular antibiotic delivery, and immune reactivation, achieving targeted therapy for P. gingivalis -infected OSCC for the very first time. • The nanoplatform offered a scalable, biocompatible, and readily translatable strategy to address pathogen-driven barriers in OSCC therapy.

Source: International Journal of Pharmaceutics X

DOI: 10.1016/j.ijpx.2025.100438