Liu Bin, Liang Shuang, Wang Zhao, Sun Qianqian, He Fei, Gai Shili, Yang Piaoping, Cheng Ziyong, Lin Jun
Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China.
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
Adv Mater. 2021 Jul;33(30):e2101223. doi: 10.1002/adma.202101223. Epub 2021 Jun 17.
Recently, enzyme dynamic therapy (EDT) has drawn much attention as a new type of dynamic therapy. However, the selection of suitable nanocarriers to deliver chloroperoxidase (CPO) and enhancement of the level of hydrogen peroxide (H O ) in the tumor microenvironment (TME) are critical factors for improving the efficiency of EDT. In this study, a rapidly decomposing nanocomposite is designed using tetra-sulfide-bond-incorporating dendritic mesoporous organosilica (DMOS) as a nanocarrier, followed by loading CPO and sodium-hyaluronate-modified calcium peroxide nanoparticles (CaO -HA NPs). The nanocomposite can effectively generate singlet oxygen ( O ) for tumor therapy without any exogenous stimulus via trimodal-enhanced EDT, including DMOS-induced depletion of glutathione (GSH), H O compensation from CaO -HA NPs in mildly acidic TME, and oxidative stress caused by overloading of Ca . As tetra-sulfide bonds are sensitive to GSH, DMOS can generate hydrogen sulfide (H S) gas as a new kind of H S gas nanoreactor. Additionally, the overloading of Ca can cause tumor calcification to accelerate in vivo tumor necrosis and promote computed tomography imaging efficacy. Therefore, a novel H S gas, EDT, and Ca -interference combined therapy strategy is developed.
最近，酶动力学疗法（EDT）作为一种新型的动力学疗法备受关注。然而，选择合适的纳米载体来递送氯过氧化物酶（CPO）以及提高肿瘤微环境（TME）中过氧化氢（H₂O₂）的水平是提高EDT效率的关键因素。在本研究中，设计了一种快速分解的纳米复合材料，使用含四硫键的树枝状介孔有机硅（DMOS）作为纳米载体，随后负载CPO和透明质酸钠修饰的过氧化钙纳米颗粒（CaO₂-HA NPs）。该纳米复合材料可通过三模态增强的EDT在无任何外源刺激的情况下有效产生单线态氧（¹O₂）用于肿瘤治疗，包括DMOS诱导的谷胱甘肽（GSH）消耗、在轻度酸性TME中CaO₂-HA NPs对H₂O₂的补充以及Ca²⁺过载引起的氧化应激。由于四硫键对GSH敏感，DMOS可作为一种新型的H₂S气体纳米反应器产生硫化氢（H₂S）气体。此外，Ca²⁺过载可导致肿瘤钙化，加速体内肿瘤坏死并提高计算机断层扫描成像效果。因此，开发了一种新型的H₂S气体、EDT和Ca²⁺干扰联合治疗策略。
