Xue Qingwen, He Ningning, Gao Yuxiu, Zhang Xuehui, Li Shuao, Chen Fang, Ning Chunping, Wu Xiaoyu, Yao Jingtong, Zhang Ziheng, Li Shangyong, Zhao Cheng
Department of Ultrasound, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People's Republic of China.
School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, 266003, People's Republic of China.
Int J Nanomedicine. 2025 Mar 6;20:2779-2796. doi: 10.2147/IJN.S505526. eCollection 2025.
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.
We manufactured DOX/BaTiO@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-NH as the liposomal membrane for ROS responsiveness, cRGD peptide for TNBC cell selectivity, and polyethylene glycol for minimized phagocytic cell absorption.
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)×10 at 12 hours post-injection.
This targeted nanocomposite material paves a new prospect for future precise piezoelectric catalytic therapy for the treatment of TNBC.
三阴性乳腺癌（TNBC）以其高恶性、有限的临床治疗选择和较差的化疗效果而闻名。尽管在使用基于纳米技术的化疗治疗TNBC方面已经取得了一些进展，但化疗药物在肿瘤部位的可控和按需释放仍然是一个挑战。
我们制备了DOX/BaTiO@cRGD-Lip（DBRL）纳米颗粒作为一种超声（US）控释平台，用于靶向递送阿霉素（DOX）以治疗TNBC。这些纳米颗粒将DSPE-Se-Se-PEG-NH纳入脂质体膜以实现对活性氧（ROS）的响应，cRGD肽用于TNBC细胞的选择性识别，以及聚乙二醇以最小化吞噬细胞的吸收。
DBRL+US组实现了显著的肿瘤抑制（与对照组相比为70.27%，p<0.001），同时在正常细胞中保持了超过90%的细胞活力，具有出色的生物相容性。在超声激活下，4T1癌细胞的细胞死亡率为55.70%，证明了其选择性细胞毒性。DBRL显示出增强的肿瘤蓄积，注射后12小时的峰值荧光强度为（1.01±0.33）×10。
这种靶向纳米复合材料为未来精确的压电催化治疗TNBC开辟了新的前景。
