Bufotalin loaded biomimetic nanodrug for combined chemo/photodynamic therapy of cancer

The combination of chemotherapy and photodynamic therapy (PDT) for enhancing cancer therapeutic efficiency has attracted tremendous attention recently. However, limitations, such as low local concentration and uncontrollable release of therapeutic agents, reduce combined treatment efficacy. In the present study, we engineered a biomimetic nanodrug employing hollow Prussian blue nanoparticles (HPB NPs) to co-load the chemical agent bufotalin (CS-5) and the photosensitizer chlorin e6 (Ce6) for combined chemo/PDT therapy against cancer. HPB NPs with catalase (CAT)-mimetic activity significantly improved the efficacy of PDT by catalyzing the decomposition of H₂O₂ into O₂, thus alleviating hypoxia, which conversely amplified the efficiency of combination therapy. <i>In vivo</i> assay demonstrated that the encapsulation of a hybrid membrane on the HPB NPs prolonged blood circulation life 3.4-fold compared to free drug. Additionally, this strategy of combinational chemo/PDT therapy exhibits a remarkable cytotoxic effect against gastric cancer (BGC-823) and breast cancer (4T1) through the induction of ferroptosis and pyroptosis while simultaneously activating the immune response, with minimal adverse effects on normal organs. Thus, the co-delivery system based on biomimetic nanocarriers appears to be a promising platform for combined chemo/PDT therapy in tumor treatment.