Cell Membrane-Liposome Hybrid Platform for Ultrasound-Activated Immune-Sonodynamic Therapy for Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a high-risk cancer, and its treatment is an important focus of biomedical research. Immuno-sonodynamic therapy (iSDT), a treatment strategy based on a combination of sonodynamic therapy (SDT) and an immune checkpoint blockade, has been proposed to achieve improved antitumor effects. In this study, chlorin e6 (Ce6) and the PD-1 inhibitor BMS202 were encapsulated into a cell membrane-camouflaged nanoliposome (Bio-Lipo-CB). SDS-PAGE assay and TEM proved the successful wrapping of cell membrane in liposomes, and Bio-Lipo-CB could selectively accumulate in 4T1 cells. Compared with Bio-Lipo-CB alone, Bio-Lipo-CB-SDT showed significant cytotoxicity with abundant ROS production and increased cell apoptosis rate. Moreover, after Bio-Lipo-CB-SDT treatment, calreticulin (CRT) extraversion to the cell membrane, HMGB1 and ATP release to extracellular, indicated immunogenic cell death (ICD). Furthermore, in vivo fluorescence imaging test showed that Bio-Lipo-CB can accumulate in the tumor site after 2 h injection. The in vivo antitumor experiment further confirmed the antitumor efficiency of Bio-Lipo-CB-SDT analysis and demonstrated that Bio-Lipo-CB-SDT induced ICD. The body weight and HE staining of normal organs primarily indicated the safety of this combined strategy. Our study is a proof of concept of synergistic tumor therapeutics based on SDT and checkpoint blockade immunotherapy using a bionic nanoplatform in TNBC.