State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin 541004, China.
Hunan Provincial Key Laboratory of Xiangnan Rare-Precious Metals Compounds Research and Application, School of Chemistry and Environmental Science, Xiangnan University, Chenzhou, 423000, China.
Nanoscale. 2023 Aug 25;15(33):13574-13582. doi: 10.1039/d3nr01971c.
Patients with β-thalassemia are prone to complications such as cardiovascular diseases and secretory gland injury due to iron overload (IO) and reactive oxygen species (ROS) production caused by blood transfusions. Simultaneously scavenging ROS and eliminating IO using nanomedicine remains challenging. Herein, we designed a dual-functional Ce-based metal-organic framework@polydopamine (Ce-MOF@PDA) composite that integrates oxidative stress reduction and IO elimination and evaluated its protective effect on IO injury in thalassemia. Using Ce-MOF with multiple active sites as the core, dopamine, which can coordinate iron ions, was modified on the surface of Ce-MOF and spontaneously polymerized to obtain PDA with iron elimination ability. Dopamine modification also adjusted the Ce/Ce ratio to further enhance the catalytic activity for scavenging ROS. Ce-MOF@PDA exhibited multiple nanozyme activities, such as superoxide dismutase- and catalase-like activities, and decreased iron-mediated oxidative stress levels . Furthermore, the serum ferritin levels and iron concentrations in the liver of IO mice were reduced following treatment with Ce-MOF@PDA, and the fecal clearance ability was comparable to that of deferoxamine. These results indicate that Ce-MOF@PDA can eliminate IO while scavenging ROS and reduce tissue damage caused by oxidative stress. Therefore, the Ce-MOF@PDA nanozyme is a promising therapeutic nanomedicine for treating thalassemia IO.
患有β-地中海贫血症的患者由于输血引起的铁过载 (IO) 和活性氧 (ROS) 产生，易发生心血管疾病和分泌腺损伤等并发症。同时利用纳米医学清除 ROS 和消除 IO 仍然具有挑战性。在此，我们设计了一种具有双重功能的基于 Ce 的金属有机骨架@聚多巴胺 (Ce-MOF@PDA) 复合材料，它集成了氧化应激减轻和 IO 消除，并评估了其对地中海贫血症 IO 损伤的保护作用。以具有多个活性位点的 Ce-MOF 为核心，表面修饰可以配位铁离子的多巴胺，多巴胺在 Ce-MOF 表面发生自聚合得到具有铁消除能力的 PDA。多巴胺修饰还调整了 Ce/Ce 比，进一步增强了清除 ROS 的催化活性。Ce-MOF@PDA 表现出多种纳米酶活性，如超氧化物歧化酶和过氧化氢酶样活性，降低了铁介导的氧化应激水平。此外，用 Ce-MOF@PDA 处理后，IO 小鼠的血清铁蛋白水平和肝脏铁浓度降低，粪便清除能力与去铁胺相当。这些结果表明，Ce-MOF@PDA 可以在清除 ROS 的同时消除 IO，并减轻氧化应激引起的组织损伤。因此，Ce-MOF@PDA 纳米酶是治疗地中海贫血症 IO 的一种很有前途的治疗性纳米医学。
