AGuIX nanoparticles enhance ionizing radiation-induced ferroptosis on tumor cells by targeting the NRF2-GPX4 signaling pathway.
AGuIX nanoparticles enhance ionizing radiation-induced ferroptosis on tumor cells by targeting the NRF2-GPX4 signaling pathway.
复制标题
AGuIX 纳米颗粒通过靶向 NRF2-GPX4 信号通路增强电离辐射诱导的肿瘤细胞铁死亡
DOI：
10.1186/s12951-022-01654-9
复制
发表时间：
2022-10-14
影响因子：
10.2
通讯作者：
Tillement, Olivier
中科院分区：
文献类型：
--
作者：
Sun, Hao;Cai, Hui;Xu, Chang;Zhai, Hezheng;Lux, Francois;Xie, Yi;Feng, Li;Du, Liqing;Liu, Yang;Sun, Xiaohui;Wang, Qin;Song, Huijuan;He, Ningning;Zhang, Manman;Ji, Kaihua;Wang, Jinhan;Gu, Yeqing;Leduc, Geraldine;Doussineau, Tristan;Wang, Yan;Liu, Qiang;Tillement, Olivier
在肿瘤放射治疗的框架内，放射抵抗仍然是一个需要解决的主要问题。为了有效提高肿瘤的放射敏感性，减少辐射对周围正常组织的损伤，放射增敏剂近年来受到越来越多的关注。作为基于金属元素Gd的纳米粒子，AGuIX纳米粒子已被证明可以增加癌症的辐射敏感性。虽然它是一种罕见的纳米材料，已经进入临床前试验，但尚不清楚的生物学机制阻碍了它的进一步临床应用。在这项研究中，我们证明了AGuIX纳米粒子对三阴性乳腺癌的放射增敏效果。我们发现，AGuIX纳米颗粒通过损害同源重组修复途径而不是非同源末端连接途径来增加DNA损伤水平。此外，实验结果表明，AGuIX纳米粒子具有诱导细胞凋亡的作用，但其诱导细胞凋亡的能力很低，不能完全解释其强烈的辐射增敏作用。铁下垂是细胞死亡的另一种方式，也被发现在辐射增敏中起重要作用，AGuIX纳米颗粒可能通过抑制NRF2-GSH-Gpx4信号通路来调节抗铁下垂系统。网上版载有补充材料，可在10.1186/s12951-022-01654-9查阅。
In the frame of radiotherapy treatment of cancer, radioresistance remains a major issue that still needs solutions to be overcome. To effectively improve the radiosensitivity of tumors and reduce the damage of radiation to neighboring normal tissues, radiosensitizers have been given increasing attention in recent years. As nanoparticles based on the metal element gadolinium, AGuIX nanoparticles have been shown to increase the radiosensitivity of cancers. Although it is a rare nanomaterial that has entered preclinical trials, the unclear biological mechanism hinders its further clinical application. In this study, we demonstrated the effectiveness of AGuIX nanoparticles in the radiosensitization of triple-negative breast cancer. We found that AGuIX nanoparticles increased the level of DNA damage by compromising the homologous recombination repair pathway instead of the non-homologous end joining pathway. Moreover, the results showed that AGuIX nanoparticles induced apoptosis, but the degree of apoptosis ability was very low, which cannot fully explain their strong radiosensitizing effect. Ferroptosis, the other mode of cell death, was also discovered to play a significant role in radiation sensitization, and AGuIX nanoparticles may regulate the anti-ferroptosis system by inhibiting the NRF2-GSH-GPX4 signaling pathway. The online version contains supplementary material available at 10.1186/s12951-022-01654-9.
登录
查看更多内容
ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
--
作者：
Brandsma I;Gent DC
通讯作者：
Gent DC
影响因子：
4.6
作者：
Detappe A;Kunjachan S;Drané P;Kotb S;Myronakis M;Biancur DE;Ireland T;Wagar M;Lux F;Tillement O;Berbeco R
通讯作者：
Berbeco R
钆基纳米颗粒 AGuIX 对非小细胞肺癌的放射增敏作用
影响因子：
9.5
作者：
Du, Yanan;Sun, Hao;Tillement, Olivier
通讯作者：
Tillement, Olivier