A biomimetic phototherapeutic nanoagent based on bacterial double-layered membrane vesicles for comprehensive treatment of oral squamous cell carcinoma

As one of the most common malignancies, oral squamous cell carcinoma (OSCC) with high rates of invasiveness and metastasis threatens people's health worldwide, while traditional therapeutic approaches have not met the requirement of its cure. Phototherapies including photothermal therapy (PTT) and photodynamic therapy (PDT) have shown great potential for OSCC treatment due to their noninvasiveness or minimal invasiveness, high selectivity and little tolerance. However, PTT or PDT alone makes it difficult to eradicate OSCC and prevent its metastasis and recurrence. Here, double-layered membrane vesicles (DMVs) were extracted from attenuated Porphyromonas gingivalis, one of the most common pathogens inside the oral region, and served as an immune adjuvant to develop a biomimetic phototherapeutic nanoagent named PBAE/IR780@DMV for OSCC treatment via combining dual PTT/PDT and robust antitumor immunity. To obtain PBAE/IR780@DMV, poly(beta-amino) ester (PBAE) was used as a carrier material to prepare the nanoparticles for loading IR780, a widely known photosensitizer possessing both PTT and PDT capabilities, followed by surface wrapping with DMVs. Upon 808 nm laser irradiation, PBAE/IR780@DMV exerted strong antitumor effects against OSCC both in vitro and in vivo, via combining PTT/PDT and specific immune responses triggered by tumor-associated antigens and DMVs. Altogether, this study provides a promising biomimetic phototherapeutic nanoagent for comprehensive treatment of OSCC. Bacterial double-layered membrane vesicles were used as an immune adjuvant to develop a biomimetic phototherapeutic nanoagent, which could exert synergistic effects of PTT/PDT and immune stimulation for OSCC comprehensive treatment.