三阴性乳腺癌（TNBC）是一种最具侵袭性、转移率高和死亡率高的肿瘤之一，占所有乳腺癌的15~20%。化疗仍然是治疗TNBC患者的主要治疗选择。我们开发了反应性氧化应激（ROS）的半乳糖化纳米颗粒（DOX@NPs）作为高效靶向载体，用于体外和体内抑制TNBC的生长。DOX@NPs由聚丙烯酸半乳糖和苯硼酸衍生物共价连接而成。研究不同配方处理的肿瘤细胞的体外细胞毒性、细胞摄取、细胞凋亡和周期分布。同时，在4T1肿瘤带瘤小鼠模型中研究体内生物分布和抗肿瘤效果。DOX@NPs显示良好的ROS响应性和H2O2存在下的快速DOX释放。此外，我们的数据表明，DOX@NPs能够有效诱导肿瘤细胞凋亡和周期停滞，高效积累在肿瘤部位，抑制肿瘤生长，并无不良副作用。我们的结果表明，DOX@NP具有作为TNBC治疗的潜在纳米载体的强大潜力，值得进一步研究其他癌症治疗。© 2023周等。

Triple negative breast cancer (TNBC) is one of the most aggressive tumors with high metastasis and mortality, which constitutes 15~20% of all breast cancers. Chemotherapy remains main therapeutic option in the treatment of patients with TNBC.We developed reactive oxygen species (ROS)-responsive galactosylated nanoparticles (DOX@NPs) as an efficiently targeted carrier for doxorubicin (DOX) delivery to inhibit the growth of TNBC in vitro and in vivo. DOX@NPs were composed of polyacrylate galactose and phenylboronic derivatives conjugation. The in vitro cytotoxicity, cellular uptake, cell apoptosis and cycle distribution of tumor cells treated with different formulations were investigated. Meanwhile in vivo biodistribution and antitumor effects were investigated in a 4T1 tumor-bearing mouse model.DOX@NPs showed good ROS responsiveness and rapid DOX release in the presence of H2O2. Furthermore, our data suggested that DOX@NPs could effectively trigger tumor cells apoptosis and cycle arrest, efficiently accumulate into tumor sites, and suppress tumor growth without adverse side effects.Our results suggested DOX@NP with potent potential as a promising nanocarrier for TNBC therapy, which deserved further investigation for other cancer treatment.© 2023 Zhou et al.