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Breaking the Redox Homeostasis: an Albumin‐Based Multifunctional Nanoagent for GSH Depletion‐Assisted Chemo‐/Chemodynamic Combination Therapy
Author(s) -
Liang Kaicheng,
Sun Haitao,
Yang Zebin,
Yu Huizhu,
Shen Jie,
Wang Xiaolin,
Chen Hangrong
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202100355
Subject(s) - glutathione , redox , reactive oxygen species , homeostasis , oxidative stress , biophysics , materials science , biochemistry , microbiology and biotechnology , chemistry , biology , enzyme , metallurgy
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.