杂志名称：Biomaterials
影响因子：12.8
文章题目：Nanomedicine-enabled concurrent regulations of ROS generation and copper metabolism for sonodynamic-amplified tumor therapy
DOI: https://doi.org/10.1016/j.biomaterials.2025.123137
第一作者：Jinhong Bing, Bangguo Zhou, Minqi Chen, Yucui Shen, Min Zhou, Han Lin, Wencheng Wu, Jianlin Shi
作者单位：
中国科学院上海陶瓷研究所高性能陶瓷和超细微结构国家重点实验室
浙江大学医学院附属第一医院
同济大学上海第四人民医院
中国电子科技大学四川省人民医院四川省医学科学院
引用YOBIBIO产品：
Phosphate buffer solution (PBS)
Roswell Park Memorial Institute (RPMI) 1640
dulbecco's modified eagle medium (DMEM)
Calcein acetoxymethyl ester (Calcein-AM)/propidium iodide (PI) staining assay
4,6-diamidino-2-phenylindole (DAPI)
Superior FBS (U11-020A)
fluorescein isothiocyanate (FITC)

文章摘要：
Sonodynamic therapy (SDT) shows substantial potentials in cancer treatment thanks to the deep tissue penetration of ultrasound. However, its clinical translation suffers from the potential damages to healthy tissues and the resistance of tumors, particularly from cancer stem-like cells (CSCs), to the ultrasound. To address these challenges, we designed a novel glutathione (GSH)-activated nanomedicine to simultaneously enhance the safety and efficacy of SDT by in situ regulating the generation of reactive oxygen species (ROS) and copper metabolism. This nanomedicine, Es@CuTCPP, was created by loading elesclomol (Es) onto CuTCPP nanosheets. By accumulating this nanomedicine in tumors, the Cu(II)-TCPP is reduced to the highly sonosensitive Cu(I)-TCPP by the intra-tumoral-overexpressed GSH, leading to the production of abundant ROS upon ultrasound exposure, which effectively kills large amounts of tumor cells. Concurrently, the released copper ions react with co-released Es to form a CuEs complex, which induces cuproptosis of CSCs surviving the ROS attack by disrupting cellular copper metabolism, evidently amplifying the effectiveness of SDT. This work presents the first paradigm of a GSH-activated and cuproptosis-enhanced SDT approach, offering a promising novel strategy for cancer therapy.

由于超声的深层组织穿透性，声动力学疗法 （SDT） 在癌症治疗中显示出巨大的潜力。然而，它的临床转化受到对健康组织的潜在损害和肿瘤的抵抗力，特别是癌症干细胞样细胞 （CSC） 对超声的抵抗力。为了应对这些挑战，我们设计了一种新型谷胱甘肽 （GSH） 活化的纳米药物，通过原位调节活性氧 （ROS） 的产生和铜代谢来同时提高 SDT 的安全性和有效性。这种纳米药物 Es@CuTCPP 是通过将 elesclomol （Es） 加载到 CuTCPP 纳米片上而制成的。通过在肿瘤中积累这种纳米药物，Cu（II）-TCPP 被肿瘤内过表达的 GSH 还原为高度对声音敏感的 Cu（I）-TCPP，导致超声暴露时产生丰富的 ROS，从而有效杀死大量肿瘤细胞。同时，释放的铜离子与共释放的 Es 反应形成 CuEs 配合物，通过破坏细胞铜代谢诱导在 ROS 攻击中幸存下来的 CSCs 的 Cuproposis，显然放大了 SDT 的有效性。这项工作提出了 GSH 激活和 cuproposisis 增强的 SDT 方法的第一个范式，为癌症治疗提供了一种有前途的新策略。