Optimizing Triple-Negative Breast Cancer Therapy via Ultrasound-Enhanced Piezocatalysis for Targeted Chemodrug Release

Introduction Triple-negative breast cancer (TNBC) is known for its high malignancy, limited clinical treatment options, and poor chemotherapy outcomes. Although some advancements have been made using nanotechnology-based chemotherapy for TNBC treatment, the controlled and on-demand release of chemotherapeutic drugs at the tumor site remains a challenge.Methods We manufactured DOX/BaTiO3@cRGD-Lip (DBRL) nanoparticles as an ultrasound (US)-controlled release platform targeting the delivery of Doxorubicin (DOX) for TNBC treatment. The nanoparticles incorporate DSPE-Se-Se-PEG-NH2 as the liposomal membrane for ROS responsiveness, cRGD peptide for TNBC cell selectivity, and polyethylene glycol for minimized phagocytic cell absorption.Results The DBRL+US group achieved significant tumor inhibition (70.27% compared to control group, p < 0.001), while maintaining excellent biocompatibility with over 90% cell viability in normal cells. The selective cytotoxicity was evidenced by a 55.70% cell death rate in 4T1 cancer cells under US activation. DBRL showed enhanced tumor accumulation with peak fluorescence intensity of (1.01 ± 0.33)×109 at 12 hours post-injection.Conclusion This targeted nanocomposite material paves a new prospect for future precise piezoelectric catalytic therapy for the treatment of TNBC.