雜志名稱：Biomaterials
影響因子：12.8
文章題目：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
作者單位：
中國科學(xué)院上海陶瓷研究所高性能陶瓷和超細(xì)微結(jié)構(gòu)國家重點實驗室
浙江大學(xué)醫(yī)學(xué)院附屬第一醫(yī)院
同濟(jì)大學(xué)上海第四人民醫(yī)院
中國電子科技大學(xué)四川省人民醫(yī)院四川省醫(yī)學(xué)科學(xué)院
引用YOBIBIO產(chǎn)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.
由于超聲的深層組織穿透性，聲動力學(xué)療法 （SDT） 在癌癥治療中顯示出巨大的潛力。然而，它的臨床轉(zhuǎn)化受到對健康組織的潛在損害和腫瘤的抵抗力，特別是癌癥干細(xì)胞樣細(xì)胞 （CSC） 對超聲的抵抗力。為了應(yīng)對這些挑戰(zhàn)，我們設(shè)計了一種新型谷胱甘肽 （GSH） 活化的納米藥物，通過原位調(diào)節(jié)活性氧 （ROS） 的產(chǎn)生和銅代謝來同時提高 SDT 的安全性和有效性。這種納米藥物 Es@CuTCPP 是通過將 elesclomol （Es） 加載到 CuTCPP 納米片上而制成的。通過在腫瘤中積累這種納米藥物，Cu（II）-TCPP 被腫瘤內(nèi)過表達(dá)的 GSH 還原為高度對聲音敏感的 Cu（I）-TCPP，導(dǎo)致超聲暴露時產(chǎn)生豐富的 ROS，從而有效殺死大量腫瘤細(xì)胞。同時，釋放的銅離子與共釋放的 Es 反應(yīng)形成 CuEs 配合物，通過破壞細(xì)胞銅代謝誘導(dǎo)在 ROS 攻擊中幸存下來的 CSCs 的 Cuproposis，顯然放大了 SDT 的有效性。這項工作提出了 GSH 激活和 cuproposisis 增強(qiáng)的 SDT 方法的第一個范式，為癌癥治療提供了一種有前途的新策略。
