Lung-targeted nanoemulsion repurpose commensal bacteria and tumor cells into in situ vaccines for treating lung cancer.

Commensal bacteria represent an influential component of lung cancer by critically affecting tumor metabolism, shaping the immunosuppressive microenvironment, and eroding therapeutic efficacy. Current antibacterial interventions for lung cancer only frame antimicrobials as adjuncts to anti-tumor therapy, failing to leverage the intrinsic adjuvant potential of tumor-resident commensal bacteria, while variable release of bacterial adjuvant components from distinct antibacterial agents and inefficient lung-targeted delivery remain unaddressed. Here, we first identified the antibacterial agent that maximizes release of bacterial adjuvant components, and co-delivered it with a potent immunogenic cell death-inducing anti-tumor drug via an ACE2-binding peptide-modified nanoemulsion to construct an "in situ vaccine" platform while inserting antibacterial and anti-tumor activities, repurposing commensal bacteria from cancer-promoting "accomplices" into immune-stimulatory "in situ adjuvant", thereby eliciting potent immune response. In vivo assays show that the modified nanoemulsion achieved efficient lung accumulation following intravenous injection, suppressed tumor growth and metastasis, eradicated commensal bacteria, reversed the immunosuppressive tumor microenvironment, and activated systemic immune responses.