NIR-responsive copper nanoliposome composites for cascaded ferrotherapy via ferroptosis actived ICD and IFN-γ released
作者全名：Wang, Junrui; Zhang, Wenli; Xie, Zhuoyan; Wang, Xingyue; Sun, Jiangshan; Ran, Fei; Jiang, Weixi; Liu, Yun; Wang, Zhigang; Ran, Haitao; Guo, Dajing
作者地址：[Wang, Junrui; Zhang, Wenli; Liu, Yun; Guo, Dajing] Chongqing Med Univ, Affiliated Hosp 2, Dept Radiol, Chongqing 400010, Peoples R China; [Wang, Junrui; Zhang, Wenli; Jiang, Weixi; Wang, Zhigang; Ran, Haitao] Chongqing Med Univ, Affiliated Hosp 2, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Wang, Junrui; Zhang, Wenli] Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing 400010, Peoples R China; [Xie, Zhuoyan] Chongqing Gen Hosp, Dept Ultrasound, Chongqing 400014, Peoples R China; [Wang, Xingyue] Hubei Univ Arts & Sci, Xiangyang Cent Hosp, Affiliated Hosp, Xiangyang 441053, Hubei, Peoples R China; [Sun, Jiangshan] Chongqing Med & Hlth Sch, Chongqing 408000, Peoples R China; [Ran, Fei] Chongqing Univ, Fuling Hosp, Dept Dent, Chongqing 408000, Peoples R China
通信作者：Guo, DJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Radiol, Chongqing 400010, Peoples R China.
来源：BIOMATERIALS
ESI学科分类：MATERIALS SCIENCE
WOS号：WOS:001231007500001
JCR分区：Q1
影响因子：12.8
年份：2024
卷号：308
期号：
开始页：
结束页：
文献类型：Article
关键词：Ferroptosis; Immunogenic ferroptosis; Cascaded therapy; Nanocomposites; Metallic biomaterials
摘要：Metallic biomaterials activate tumor ferroptosis by increasing oxidative stress, but their efficacy is severely limited in tumor microenvironment. Although interferon gamma (IFN-gamma) can promote tumor ferroptosis sensitivity by inhibiting the antioxidant system and promoting lipid accumulation, this effect limited by the lack of IFN-gamma accumulation in tumors. Herein, we report a near-infrared (NIR)-responsive HCuS nanocomposite (HCuSPE@TSL-tlyp-1) that can stimulate immunogenic cell death (ICD)-mediated IFN-gamma secretion through exogenous oxidative stress, thereby achieving cascaded ferrotherapy by mutually reinforcing ferroptosis and systemic immunity. Upon laser irradiation, the dissolution of the thermal coating, and the introduction of Cu ions and piperazine-erastin (PE) simultaneously induce oxidative stress by reactive oxygen species (ROS)/lipid peroxide (LPO) accumulation and deplete cystine-glutamate transporter (xCT)/GSH. The onset of oxidative stressmediated ferroptosis is thus achieved, and ICD is triggered, significantly promoting cytotoxic T-cell (CTL) infiltration for IFN-gamma secretion. Furthermore, IFN-gamma induces immunogenic tumor ferroptosis by inhibiting xCTantioxidant pathways and enhancing the ACSL4-fatty acid recruitment pathway, which further promotes sensitivity to ferroptosis in cells. These HCuS nanocomposites combined with aPD-L1 effectively in inhibiting tumor metastasis and recurrence. Importantly, these cascade ferrotherapy results broadens the application of HCuS biomaterials.
基金机构：Chongqing [cstc2021ycjh-bgzxm0168]
基金资助正文：The authors are sincerely grateful for financial support from the Natural Science Foundation Project (Grant Nos. 82271970, 81971608 and 81903561) . This work was supported by Postdoctoral Innovation Talents Support Program of Chongqing (CQBX202303) , the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (No.CQYC2020030389, 2020-7) and Talent Program of Chongqing (cstc2021ycjh-bgzxm0168) .r Chongqing (cstc2021ycjh-bgzxm0168) .
