清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

An iron oxyhydroxide-based nanosystem sensitizes ferroptosis by a “Three-Pronged” strategy in breast cancer stem cells

脂质过氧化 GPX4 程序性细胞死亡 细胞凋亡 癌症研究 癌细胞 谷胱甘肽 干细胞 化学 癌症干细胞 癌症 抗氧化剂 谷胱甘肽过氧化物酶 细胞生物学 生物化学 生物 医学 内科学
作者
Kai Wu,Wei Zhang,Hao Chen,Jie Wu,Xiaotong Wang,Xinjian Yang,Xing‐Jie Liang,Jinchao Zhang,Dandan Liu
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:160: 281-296 被引量:3
标识
DOI:10.1016/j.actbio.2023.02.015
摘要

The anti-apoptotic mechanism of breast cancer stem cells (BCSCs) makes it an obstacle to traditional apoptosis as the primary way of death. Ferroptosis is a recently reported mode of programmed cell death caused by the accumulation of iron-dependent lipid peroxidation (LPO) in cells. High dependence on iron makes BCSCs more sensitive to ferroptosis. However, the high level of the Prominin2 protein and high concentration of GSH in BCSCs make BCSCs able to efflux excess iron ions and clear LPO, which limits the therapeutic efficacy of ferroptosis in BCSCs. To overcome this obstacle, we designed a hyaluronic acid (HA)-coated siProminin2-loaded FeOOH nanoparticle (FeOOH/siPROM2@HA) to amplify ferroptosis. The FeOOH/siPROM2@HA is stable under physiologically neutral conditions but generates Fe3+ in an acidic microenvironment; meanwhile, the released siProminin2 inhibits its efflux, and then Fe3+ undergoes a redox reaction with endogenous GSH to produce Fe2+, which initiates the Fenton reaction-based ferroptosis by LPO elevation. Both in vitro and in vivo studies showed that these pH-sensitive NPs significantly inhibited tumor growth by downregulating glutathione peroxidase 4 (GPX4). Overall, this work demonstrates a "three-pronged" strategy for amplified ferroptotic therapy by simultaneously promoting intracellular iron, inhibiting iron efflux, and depleting GSH, which presents a potential strategy for CSC-targeted cancer therapy. STATEMENT OF SIGNIFICANCE: As the root of recurrence and metastasis, breast cancer stem cells (BCSCs) are resistant to traditional apoptotic death, so it is urgent to explore a new death mode for BCSCs. It has been reported that BCSCs are highly iron-dependent and, therefore, more sensitive to ferroptosis; however, the therapeutic efficacy is greatly limited by the overexpression of Prominin2 in BCSCs, which is correlated with resistance to ferroptosis by exocytosis of iron ions. In this work, we designed a hyaluronic acid-coated siProminin2-loaded FeOOH nano-drug (FeOOH/siPROM2@HA) to accelerate ferroptosis of BCSCs by simultaneously increasing iron ion content, inhibiting iron efflux, and scavenging GSH. This "three-pronged" strategy has significant implications for BCSC-targeted cancer therapy.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
18秒前
慕青应助科研通管家采纳,获得10
29秒前
1分钟前
悦悦完成签到,获得积分10
1分钟前
even完成签到 ,获得积分10
2分钟前
liguanyu1078完成签到,获得积分10
2分钟前
捉迷藏应助科研通管家采纳,获得10
2分钟前
沉沉完成签到 ,获得积分0
2分钟前
河豚发布了新的文献求助10
2分钟前
拓跋雨梅完成签到 ,获得积分0
3分钟前
XQL完成签到 ,获得积分10
3分钟前
4分钟前
滕皓轩完成签到 ,获得积分10
5分钟前
WXM完成签到 ,获得积分10
6分钟前
6分钟前
清净126完成签到 ,获得积分10
7分钟前
老宇126完成签到,获得积分10
8分钟前
应夏山完成签到 ,获得积分10
8分钟前
清净163完成签到,获得积分10
8分钟前
觀海聴濤完成签到 ,获得积分10
9分钟前
紫熊完成签到,获得积分10
9分钟前
巫巫巫巫巫完成签到 ,获得积分10
11分钟前
娟儿完成签到 ,获得积分10
11分钟前
Robin95完成签到 ,获得积分10
11分钟前
和谐的夏岚完成签到 ,获得积分10
12分钟前
菲菲完成签到 ,获得积分10
13分钟前
lili发布了新的文献求助10
14分钟前
草帽女孩完成签到 ,获得积分10
14分钟前
imi完成签到 ,获得积分10
14分钟前
lili完成签到,获得积分10
15分钟前
aniu完成签到 ,获得积分10
15分钟前
amar完成签到 ,获得积分10
16分钟前
naczx完成签到,获得积分10
16分钟前
正直的宛秋完成签到 ,获得积分10
18分钟前
稻子完成签到 ,获得积分10
19分钟前
20分钟前
冰释之川完成签到 ,获得积分10
20分钟前
clare完成签到 ,获得积分10
20分钟前
如意完成签到 ,获得积分10
21分钟前
轻松的尔风完成签到 ,获得积分10
22分钟前
高分求助中
Un calendrier babylonien des travaux, des signes et des mois: Séries iqqur îpuš 1036
Sustainable Land Management: Strategies to Cope with the Marginalisation of Agriculture 1000
Corrosion and Oxygen Control 600
Python Programming for Linguistics and Digital Humanities: Applications for Text-Focused Fields 500
Heterocyclic Stilbene and Bibenzyl Derivatives in Liverworts: Distribution, Structures, Total Synthesis and Biological Activity 500
重庆市新能源汽车产业大数据招商指南(两链两图两池两库两平台两清单两报告) 400
Division and square root. Digit-recurrence algorithms and implementations 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2545822
求助须知:如何正确求助?哪些是违规求助? 2175672
关于积分的说明 5600226
捐赠科研通 1896383
什么是DOI,文献DOI怎么找? 946268
版权声明 565379
科研通“疑难数据库(出版商)”最低求助积分说明 503557