An active-passive strategy for enhanced synergistic photothermal-ferroptosis therapy in the NIR-I/II biowindows
An active-passive strategy for enhanced synergistic photothermal-ferroptosis therapy in the NIR-I/II biowindows
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NIR-I/II 生物窗口中增强协同光热铁死亡治疗的主动-被动策略
DOI：
10.1039/d1bm01908b
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发表时间：
2022
影响因子：
6.6
通讯作者：
Yulei Chang
中科院分区：
文献类型：
--
作者：
Fengxia Wu;Haoran Chen;Ruiqi Liu;Yongkuan Suo;Qiqing Li;Youlin Zhang;Hongguang Liu;Zhen Cheng;Yulei Chang
铁下垂治疗(FT)是一种通过过氧化脂质(LPO)过度积聚来选择性损伤癌细胞的有吸引力的策略。然而，由于肿瘤微环境(TME)中有限的Fenton反应效率和进化的内在耐药机制，该疗法的疗效较差。新型铁性下垂诱导剂的开发对提高FT的疗效具有重要意义。在这里，我们开发了一种片状的Bi2Se3-Fe3O4/Au(BFA)热敏纳米平台，它可以加快Fenton反应的速度，以主动-被动的方式增强FT。在Fe3O4纳米粒子和Au纳米粒子的内部协同作用和外部近红外热疗的作用下，BFA纳米粒子可以促进羟基自由基(·OH)的产生，从而增强细胞内的氧化应激，并通过灭活谷胱甘肽过氧化物酶4(Gpx4)而进一步诱导铁下垂。此外，BFA纳米粒子在NIR-I和NIR-II窗口都显示出很高的光热转换效率(在808 nm和1064 nm分别为66.2%和58.2%)；因此，作为光热剂(PTA)，它们也可以通过近红外触发的光热疗法(PTT)直接烧蚀癌细胞。同时，BFA纳米粒子可作为光声(PA)/磁共振(MR)/X射线成像的有效诊断试剂，指导光热-铁下垂的协同治疗。因此，BFA NP介导的增强型光热-铁下垂治疗为纳米材料在肿瘤治疗中的应用提供了一种很有前途的策略。
Ferroptosis therapy (FT) is an attractive strategy to selectively damage cancer cells through lipid peroxide (LPO) over-accumulation. However, this therapy suffers from poor therapeutic efficacy due to the limited Fenton reaction efficiency and the evolved intrinsic resistance mechanism in the tumor microenvironment (TME). The exploitation of novel ferroptosis inducers is of significance for improving the efficacy of FT. Here, we develop a plate-like Bi2Se3–Fe3O4/Au (BFA) theranostic nanoplatform, which can increase the Fenton reaction rate to enhance FT in an active-passive way. In detail, benefiting from the internal synergistic effect of Fe3O4 NPs and Au NPs and external NIR-mediated hyperthermia, the BFA NPs can boost hydroxyl radical (˙OH) generation to enhance intracellular oxidative stress and further induce ferroptosis by inactivating glutathione peroxidase 4 (GPX4). Furthermore, the BFA NPs show high photothermal conversion efficiency in both the NIR-I and NIR-II windows (66.2% at 808 nm and 58.2% at 1064 nm, respectively); therefore, as a photothermal agent (PTA), they can also ablate cancer cells directly by NIR-triggered photothermal therapy (PTT). Meanwhile, BFA NPs could be used as an efficient diagnostic agent for photoacoustic (PA)/magnetic resonance (MR)/X-ray imaging to guide the synergistic therapy of photothermal-ferroptosis. Therefore, BFA NP-mediated enhanced photothermal-ferroptosis therapy represents a promising strategy for the application of nanomaterials in tumor therapy.