A Bacterial Nanomedicine Combines Photodynamic‐Immunotherapy and Chemotherapy for Enhanced Treatment of Oral Squamous Cell Carcinoma

Abstract Bacterial therapy is an emerging hotspot in tumor immunotherapy, which can initiate antitumor immune activation through multiple mechanisms. Porphyromonas gingivalis (Pg), a pathogenic bacterium inhabiting the oral cavity, contains a great deal of pathogen associated molecular patterns that can activate various innate immune cells to promote antitumor immunity. Owing to the presence of protoporphyrin IX (PpIX), Pg is also an excellent photosensitizer for photodynamic therapy (PDT) via the in situ generation of reactive oxygen species. This study reports a bacterial nanomedicine (nmPg) fabricated from Pg through lysozyme degradation, ammonium chloride lysis, and nanoextrusion, which has potent PDT and immune activation performances for oral squamous cell carcinoma (OSCC) treatment. To further promote the tumoricidal efficacy, a commonly used chemotherapeutic drug doxorubicin (DOX) is efficiently encapsulated into nmPg through a simple incubation method. nmPg/DOX thus prepared exhibits significant synergistic effects on inhibiting the growth and metastasis of OSCC both in vitro and in vivo via photodynamic‐immunotherapy and chemotherapy. In summary, this work develops a promising bacterial nanomedicine for enhanced treatment of OSCC.