摘要
铁死亡是一种铁依赖性活性氧异常堆积而导致氧化还原平稳失调的细胞死亡方式。作为一种新的癌症治疗途径,铁死亡引起了研究者的广泛关注。随着纳米科学的迅速发展,多样化的功能性纳米材料能够发挥生成过氧化氢,清除谷胱甘肽,以及提供芬顿反应催化剂等作用,因此能够协同所负载的铁死亡诱导药物而发挥出更加强大的肿瘤抑制作用。本文首先介绍了铁死亡的发生机制及铁死亡诱导策略在肿瘤治疗中的可行性。其次,概述了铁死亡诱导型纳米药物的构建思路,主要包括:加速细胞内芬顿反应、抑制谷胱甘肽过氧化物酶4的活性及增加脂质过氧化物的外源递送。此外,本文还总结了基于铁死亡的联合疗法,包括与传统疗法的联合治疗(联合凋亡诱导药物、免疫治疗与基因治疗)以及体外能量协同诱导铁死亡治疗(包括超声治疗及光动力治疗)。最后,本文讨论了未来诱导铁死亡纳米药物在癌症治疗中的期望和挑战。
Ferroptosis is a cell death path for the abnormal accumulation of iron dependent reactive oxygen species,which leads to the dysregulation of redox homeostasis.As a new type of cancer treatments,ferroptosis has attracted extensive attention of researchers.With the development of nanoscience,various functional nanomaterials can produce H2O2,exhaust glutathione,and gather Fenton reaction catalysts in tumor site.Therefore,these nanoma‐terials can play a stronger role in tumor inhibition in coordination with the ferroptosis-inducing agents.Firstly,this paper introduced the mechanism of ferroptosis and the feasibility of ferroptosis-inducing strategy in cancer therapy.Secondly,we summarized the construction strategies of the ferroptosis-inducing nanomedicines for cancer therapy,including accelerating intracellular Fenton reaction,inhibiting the activity of glutathione peroxidase 4,and increasing the exogenous delivery of lipid peroxides.In addition,we also discussed the combination therapy based on ferrop‐tosis,including the combination of ferroptosis with traditional therapy strategies(combined with apoptosis-inducing drugs,immunotherapy and gene therapy)and external energy(including ultrasound therapy and photodynamic therapy).Finally,the expectations and challenges of ferroptosis-inducing nanomedicines for cancer therapy in the future were discussed.
作者
李超群
汤红霞
张悦
宋倩倩
陈凤英
费伟东
LI Chao-qun;TANG Hong-xia;ZHANG Yue;SONG Qian-qian;CHEN Feng-ying;FEI Wei-dong(College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;Department of Pharmacy,Women's Hospital,School of Medicine,Zhejiang University,Hangzhou 310006,China)
出处
《药学学报》
CAS
CSCD
北大核心
2020年第9期2099-2109,共11页
Acta Pharmaceutica Sinica
基金
浙江省自然科学基金资助项目(LQ20H300002).
关键词
铁死亡
纳米药物
活性氧
谷胱甘肽过氧化物酶4
联合治疗
ferroptosis
nanomedicine
reactive oxygen species
glutathione peroxidase 4
combination therapy
