Probiotics-Driven Type I Photosensitizer for Tumor-Targeted Fluorescence Imaging and Photodynamic Immunotherapy

Abstract The high morbidity and mortality of cancer have driven the medical community to continuously explore strategies for diagnosis and treatment. Photosensitizers (PSs) offer the possibility of simultaneous diagnosis and photodynamic therapy (PDT) for tumors with the advantages of noninvasiveness, high sensitivity, and minimum drug resistance. However, current PSs lack active tumor-targeting capability and systemic antitumor immune activity, leading to poor diagnostic and therapeutic efficacy, which remains a major challenge in cancer theranostics. To address this issue, a boric acid-functionalized type I PS-engineered probiotic (E. coli@ACR-DMP) was developed for tumor-targeted fluorescence diagnosis and photodynamic immunotherapy. This system leverages the natural tumor hypoxia tropism of Escherichia coli (E. coli) for driving tumor targeting and further responds to the acidic tumor microenvironment to trigger PS release for fluorescence diagnosis and photodynamic ablation of the tumor. Furthermore, the pathogen-associated molecular patterns (PAMPs) synergize with PDT-induced immunogenic cell death to promote dendritic cell maturation and T-cell infiltration, converting local phototherapy into systemic antitumor immune activation. In a 4T1 tumor-bearing mouse model, E. coli@ACR-DMP exhibits excellent tumor-targeting ability, which enables its use in tumor fluorescence diagnosis and photodynamic inhibition of tumor growth along with activated antitumor immunity. This work provides a covalent bacteria-based delivery platform, offering a promising strategy for precision cancer therapeutics.