L-buthionine sulfoximine encapsulated hollow calcium peroxide as a chloroperoxidase nanocarrier for enhanced enzyme dynamic therapy. (October 2022)

• Record Type: Journal Article
• Authors: Liu, Bin; Bian, Yulong; Yuan, Meng; Zhu, Yanlin; Liu, Shikai; Ding, He; Gai, Shili; Yang, Piaoping; Cheng, Ziyong; Lin, Jun
• Is Part Of: Biomaterials. Volume 289(2022)
• Publication Date: 2022-10
• Subjects: One-step synthesis -- Hollow calcium peroxide -- L-buthionine sulfoximine -- Multifunctional nanocarrier -- Enzyme dynamic therapy; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2022.121746
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: 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 Ca 2+, BSO molecules, CPO, and concurrently generates a large volume of hydrogen peroxide (H2 O2 ) 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 H2 O2, the EDT efficiency of CPO was significantly enhanced to achieve high tumor therapy efficiency. Additionally, overloaded Ca 2+ 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. Graphical abstract: Image 1 Highlights: One-step synthesis of multifunctional nanocarrier for CPO delivery. The nanocomposite can rapidly decompose through acid and HAD-response in TME. GSH depletion, self-supplying H2 O2, overloaded Ca 2+ -induced mitochondria damage. The efficacy of EDT could be triply improved. Calcification accelerates tumor apoptosis and enhances CT imaging efficacy.