MR imaging guided iron-based nanoenzyme for synergistic Ferroptosis−Starvation therapy in triple negative breast cancer
MR imaging guided iron-based nanoenzyme for synergistic Ferroptosis−Starvation therapy in triple negative breast cancer
复制标题
磁共振成像引导铁基纳米酶用于三阴性乳腺癌的协同铁死亡和饥饿疗法
DOI：
10.1016/j.smaim.2021.12.008
复制
发表时间：
2021-12
影响因子：
--
通讯作者：
Xiao Zeyu
中科院分区：
文献类型：
--
作者：
Wang Duo;Fang Weimin;Huang Cuiqing;Chen Zerong;Nie Tianqi;Wang Jinghao;Luo Liangping;Xiao Zeyu
三阴性乳腺癌（Triple Negative Breast Cancer，TNBC）是乳腺癌中侵袭性最强的一种，是世界范围内女性死亡的主要原因。由于相关激素受体的缺乏，激素治疗TNBC的疗效在临床上受到很大限制。铁凋亡是一种新出现的抗肿瘤策略，通过提高铁依赖性脂质过氧化物水平诱导癌细胞死亡，而不需要细胞受体介导，已被证明在各种癌症治疗中是可行的。然而，肿瘤微环境中的高谷胱甘肽（GSH）水平限制了铁凋亡的抗肿瘤功效。本文设计并成功制备了Avastin（Ava）修饰的超顺磁性氧化铁（SPIO）纳米酶，用于TNBC的协同铁凋亡和饥饿治疗。通过下调GSH和谷胱甘肽过氧化物酶4（GPX 4），所制备的基于SPIO的纳米酶有效地提高了对MDA-MB-231细胞的铁凋亡功效。此外，基于Ava修饰的饥饿疗法的整合大大降低了CD 31的表达，导致营养缺乏状态，从而以协同方式显著增强了铁凋亡功效。从MDA-MB-231细胞异种移植小鼠模型的抗肿瘤研究中得出结论，全身施用该纳米酶有效地抑制了肿瘤生长，并成功地提高了小鼠存活率。总的来说，我们相信这种生物相容的协同性铁中毒-饥饿纳米酶可以为TNBC的临床治疗提供新的范围。
Triple negative breast cancer (TNBC), as the most aggressive BC, accounts for the leading cause of worldwide women death. Owing to the deficiency of related hormone receptors, the efficacy of hormone therapy on TNBC is significantly confined in clinical treatment. Ferroptosis, a newly emerging antitumor strategy through enhancing iron-dependent lipid peroxides level to induce cancer cell death without the mediation of cell receptors, has been proved to be feasible in various cancer treatments. However, the high glutathione (GSH) level in tumor microenvironment limits the anti-tumor efficacy of ferroptosis. Herein, superparamagnetic iron oxide (SPIO) based nanoenzyme modified with Avastin (Ava) was designed and successfully prepared for synergistic ferroptosis and starvation therapy of TNBC. Through downregulating the GSH and glutathione peroxidase 4 (GPX4), the as-prepared SPIO-based nanoenzyme efficiently improved the ferroptosis efficacy on MDA-MB-231 cells. Besides that, the integration of starvation therapy based on Ava modification greatly decreased the expression of CD31, resulted to a nutrient-deprived status and thus significantly enhanced ferroptosis efficacy in a synergistic manner. Concluded from the antitumor investigation on an MDA-MB-231 cells xenograft mice model, the systemic administration of this nanoenzyme effectively inhibited the tumor growth and successfully enhanced the mice survival rate. Overall, we believe this biocompatible synergistic ferroptosis-starvation nanoenzyme may provide a refreshing scope to the clinical treatment of TNBC.
登录
查看更多内容
精确交付用于 MRI 引导癌症治疗的多功能纳米系统，并通过功能扩散加权 MRI 监测肿瘤反应
影响因子：
7
作者：
Xiao, Zeyu;Chan, Leung;Luo, Liangping
通讯作者：
Luo, Liangping
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：
16.6
作者：
Wang G;Xie L;Li B;Sang W;Yan J;Li J;Tian H;Li W;Zhang Z;Tian Y;Dai Y
通讯作者：
Dai Y
DOI：
10.1126/science.aaw9872
发表时间：
2020-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badgley MA;Kremer DM;Maurer HC;DelGiorno KE;Lee HJ;Purohit V;Sagalovskiy IR;Ma A;Kapilian J;Firl CEM;Decker AR;Sastra SA;Palermo CF;Andrade LR;Sajjakulnukit P;Zhang L;Tolstyka ZP;Hirschhorn T;Lamb C;Liu T;Gu W;Seeley ES;Stone E;Georgiou G;Manor U;Iuga A;Wahl GM;Stockwell BR;Lyssiotis CA;Olive KP
通讯作者：
Olive KP
多功能纳米治疗剂增强厄洛替尼对 EGFR 野生型非小细胞肺癌的治疗作用
影响因子：
18.9
作者：
Wang D;Zhou J;Fang W;Huang C;Chen Z;Fan M;Zhang MR;Xiao Z;Hu K;Luo L
通讯作者：
Luo L