Breaking the Redox Homeostasis: an Albumin‐Based Multifunctional Nanoagent for GSH Depletion‐Assisted Chemo‐/Chemodynamic Combination Therapy

谷胱甘肽 平衡 化学 氧化还原 氧化应激 活性氧 生物化学 材料科学 生物物理学 细胞生物学 生物 冶金
作者
Kaicheng Liang,Haitao Sun,Zebin Yang,Huizhu Yu,Jie Shen,Xiaolin Wang,Hangrong Chen
出处
期刊:Advanced Functional Materials [Wiley]
卷期号:31 (22) 被引量:73
标识
DOI:10.1002/adfm.202100355
摘要

Abstract Redox homeostasis is vital for cell survival. Nowadays, developing novel nanoagents that can efficiently break the redox homeostasis, which includes improving the reactive oxygen species level while reducing the glutathione (GSH) level, has emerged as a promising but challenging strategy for tumor therapy. In this work, a novel albumin‐based multifunctional nanoagent is developed for GSH‐depletion assisted chemo‐/chemodynamic combination therapy. Briefly, CuO and MnO X are in situ co‐grown inside the albumin molecules through a facile biomineralization process, followed by the conjugation of Pt (IV) prodrug to obtain the final nanoagent. Thereinto, copper species can produce •OH with optimal efficiency under weakly acidic conditions (pH = 6.5), while MnO X can react with GSH, leading to the GSH depletion, which reduces the formation of GSH‐Pt adducts and •OH consumption, thus favoring a better chemotherapy and chemodynamic therapy effect, respectively. Significantly, both GSH depletion and •OH generation contributes to the inhibited expression of GPX‐4, which further increases the oxidative stress. Moreover, during the reaction between MnO X and GSH or H 2 O 2 , Mn 2+ ions are released for MR imaging while O 2 is produced for hypoxia relief. It is believed that the proposed strategy can provide a new perspective on effective tumor therapy.
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