L-buthionine sulfoximine encapsulated hollow calcium peroxide as a chloroperoxidase nanocarrier for enhanced enzyme dynamic therapy

丁硫胺 纳米载体 材料科学 谷胱甘肽 生物物理学 过氧化氢 氧化应激 药物输送 化学 生物化学 纳米技术 生物 冶金
作者
Bin Liu,Yulong Bian,Meng Yuan,Yanlin Zhu,Shikai Liu,He Ding,Shili Gai,Piaoping Yang,Ziyong Cheng,Jun Lin
出处
期刊:Biomaterials [Elsevier]
卷期号:289: 121746-121746 被引量:20
标识
DOI:10.1016/j.biomaterials.2022.121746
摘要

The appropriate design of multifunctional nanocarriers for chloroperoxidase (CPO) delivery and the simultaneous improvement of the efficiency of enzyme dynamic therapy (EDT) remain significant challenges. Herein, we report a facile one-step route to obtain a multifunctional nanocarrier for the formation of sodium hyaluronate-modified hollow calcium peroxide spheres with encapsulated L-buthionine sulfoximine (BSO), followed by delivery of CPO for enhanced EDT. After effective accumulation at the tumor sites, the nanocomposite rapidly decomposes and releases Ca2+, BSO molecules, CPO, and concurrently generates a large volume of hydrogen peroxide (H2O2) in the endogenous tumor microenvironment (TME). BSO molecules inhibit the biosynthesis of glutathione (GSH) by inactivating γ-glutamyl cysteine synthetase. Due to BSO-induced GSH depletion and self-supply of H2O2, the EDT efficiency of CPO was significantly enhanced to achieve high tumor therapy efficiency. Additionally, overloaded Ca2+ caused mitochondrial damage and amplified the oxidative stress. Moreover, calcification resulted from the unbalanced calcium transport channel caused by enhanced oxidative stress, accelerating tumor apoptosis and improving the efficacy of computed tomography (CT) imaging visual tumor therapy. This simple and efficient design for multifunctional nanocomposites will likely take an important place in the field of combined tumor therapeutics.
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