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

Qingwen Xue,1,&ast; Ningning He,2,&ast; Yuxiu Gao,1 Xuehui Zhang,1 Shuao Li,1 Fang Chen,1 Chunping Ning,1 Xiaoyu Wu,2 Jingtong Yao,2 Ziheng Zhang,2 Shangyong Li,1,2 Cheng Zhao1 1Department of Ultrasound, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, 266003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng Zhao; Shangyong Li, Email [email protected]; [email protected]: 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.Keywords: sonodynamic therapy, chemotherapy, triple-negative breast cancer, drug delivery, ultrasound