1. l-Buthionine Sulfoximine Detection and Quantification in Polyurea Dendrimer Nanoformulations
Pedro Mota, Rita F Pires, Jacinta Serpa, Vasco D B Bonifácio Molecules. 2019 Aug 27;24(17):3111. doi: 10.3390/molecules24173111.
l-Buthionine sulfoximine (l-BSO) is an adjuvant drug that is reported to increase the sensitivity of cancer cells to neoplastic agents. Dendrimers are exceptional drug delivery systems and l-BSO nanoformulations are envisaged as potential chemotherapeutics. The absorption of l-BSO at a low wavelength limits its detection by conventional analytical tools. A simple and sensitive method for l-BSO detection and quantification is now reported. In this study, l-BSO was encapsulated in a folate-targeted generation four polyurea dendrimer (PUREG4-FA2) and its release profile was followed for 24 h at pH 7.4 and 37 °C. The protocol uses in situ l-BSO derivatization, by the formation of a catechol-derived orto-quinone, followed by visible detection of the derivative at 503 nm. The structure of the studied l-BSO derivative was assessed by NMR spectroscopy.
2. Buthionine sulfoximine, an experimental tool to induce glutathione deficiency: elucidation of glutathione and ascorbate in their role as antioxidants
H P Broquist Nutr Rev. 1992 Apr;50(4 ( Pt 1)):110-1. doi: 10.1111/j.1753-4887.1992.tb01298.x.
The development of buthionine sulfoximine, a selective inhibitor of glutathione biosynthesis, is an important new tool to elucidate the in vivo role of glutathione. Recent investigations have shown that ascorbic acid can serve as an essential antioxidant in the presence of severe glutathione deficiency.
3. L-buthionine sulfoximine encapsulated hollow calcium peroxide as a chloroperoxidase nanocarrier for enhanced enzyme dynamic therapy
Bin Liu, Yulong Bian, Meng Yuan, Yanlin Zhu, Shikai Liu, He Ding, Shili Gai, Piaoping Yang, Ziyong Cheng, Jun Lin Biomaterials. 2022 Oct;289:121746. doi: 10.1016/j.biomaterials.2022.121746. Epub 2022 Sep 2.
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.
