Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China; Key Laboratory of In-Fiber Integrated Optics of Ministry of Education, College of Physics and Optoelectronic Engineering, Harbin Engineering University, Harbin, 150001, PR China.
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China.
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 Ca, BSO molecules, CPO, and concurrently generates a large volume of hydrogen peroxide (HO) 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 HO, the EDT efficiency of CPO was significantly enhanced to achieve high tumor therapy efficiency. Additionally, overloaded Ca 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.
多功能纳米载体的合理设计用于递送氯化过氧化物酶（CPO）并同时提高酶动力学治疗（EDT）的效率仍然是重大挑战。在此，我们报告了一种简便的一步法途径，可获得多功能纳米载体，用于形成具有包裹的 L-丁硫氨酸亚砜（BSO）的透明质酸钠修饰的中空过氧化钙球，随后递送 CPO 以增强 EDT。在有效积聚在肿瘤部位后，纳米复合材料迅速分解并释放 Ca、BSO 分子、CPO，并同时在内在的肿瘤微环境（TME）中产生大量的过氧化氢（HO）。BSO 分子通过使γ-谷氨酰半胱氨酸合成酶失活来抑制谷胱甘肽（GSH）的生物合成。由于 BSO 诱导的 GSH 耗竭和 HO 的自我供应，CPO 的 EDT 效率显著提高，从而实现了高肿瘤治疗效率。此外，过量的 Ca 引起线粒体损伤并放大了氧化应激。此外，由于增强的氧化应激导致钙转运通道失衡而引起的钙化，加速了肿瘤细胞凋亡并提高了计算机断层扫描（CT）成像视觉肿瘤治疗的效果。这种用于多功能纳米复合材料的简单而高效的设计很可能在联合肿瘤治疗领域占据重要地位。
