Abstract

Bacterial outer membrane vesicles (OMVs) have emerged as promising platforms for cancer therapy owing to their intrinsic biological activity and capacity for drug loading. Herein, we developed a multifunctional OMV-based nanoreactor (T-TiCNOMV-GL) for enhanced photodynamic therapy (PDT) against breast cancer by integrating OMV purification, tumor targeting, metabolic depletion, and photodynamically driven self-propulsion. Titanium carbonitride (TiCN) was selected as the photosensitizer because of its strong affinity for OMVs and efficient absorption of near-infrared light, enabling robust photodynamic reactions. To improve tumor specificity, the homing peptide LyP1 was conjugated to the membrane protein cytolysin A. In addition, self-expressed lactate oxidase and exogenously supplied glucose oxidase were incorporated into the nanoreactor to deplete lactate and glucose within the tumor microenvironment while generating hydrogen peroxide to amplify PDT efficacy. In vitro experiments demonstrated that T-TiCNOMV-GL significantly inhibited the viability, proliferation, migration, and colony-forming ability of 4T1 breast cancer cells. In vivo, treatment markedly suppressed tumor growth and increased serum levels of pro-inflammatory cytokines. Transcriptomic analysis further revealed that, beyond inducing oxidative stress, T-TiCNOMV-GL promotes tumor cell apoptosis through the regulation of immune-related key genes. Collectively, these findings demonstrate the successful construction of a multifunctional OMV-based nanoplatform with enhanced antitumor efficacy, highlighting its potential for breast cancer PDT.