肿瘤微环境
巨噬细胞
活性氧
糖酵解
化学
肿瘤进展
信号转导
癌症研究
炎症
氧化应激
线粒体
细胞生物学
生物
免疫学
生物化学
体外
新陈代谢
肿瘤细胞
基因
作者
Zhengying Gu,Tianqing Liu,Chao Liu,Yannan Yang,Jie Tang,Hao Song,Yue Wang,Yang Yang,Chengzhong Yu
出处
期刊:Nano Letters
[American Chemical Society]
日期:2021-07-22
卷期号:21 (15): 6471-6479
被引量:68
标识
DOI:10.1021/acs.nanolett.1c01401
摘要
Modulation of tumor-associated macrophages (TAMs) holds promise for cancer treatment, mainly relying on M1 signaling activation and pro-inflammatory promotion. Nevertheless, the antitumor activity is often limited by the anti-inflammatory factors in the tumor microenvironment. Moreover, the metabolic function of TAMs is also critical to tumor progression. However, there are a few strategies that can simultaneously regulate both inflammatory and metabolic functions to achieve safe and potent antitumor activation of TAMs. Herein, we demonstrate that an iron-based metal organic framework nanoparticle and a ferroptosis-inducing agent synergistically induce mitochondrial alternation in TAMs, resulting in a radical metabolic switch from mitochondrial oxidative phosphorylation to glycolysis, which is resistant to anti-inflammatory stimuli challenge. The ferroptosis stress strengthened by the nanoformulation also drives multiple pro-inflammatory signaling pathways, enabling macrophage activation with potent tumoricidal activities. The ferroptosis-strengthened macrophage regulation strategy present in this study paves the way for TAM-centered antitumoral treatment to overcome the limitations of conventional methods.
科研通智能强力驱动
Strongly Powered by AbleSci AI