Ma Ying, Tu Yixing, Chen Yang, Chen Xinyi, Pan Xier, Sun Mingyue, Fu Xiuzhi, Zou Jiafeng, Gao Feng
Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
ACS Appl Mater Interfaces. 2025 Jan 8;17(1):617-631. doi: 10.1021/acsami.4c17782. Epub 2024 Dec 25.
Inflammatory bowel disease involves excess reactive oxygen species (ROS) and hydrogen sulfide (HS) at inflammatory sites. Nanozyme-mediated ROS and HS scavenging therapy is promising for colitis treatment. Here, we synthesized a multiple ROS scavenging CuO nanoparticle and first explored its HS scavenging capacity. Chitosan oligosaccharide modified with alpha-lipoic acid was coated on the nanoparticles to further enhance the HS scavenging capacity. Furthermore, calcium alginate was coated on the surface to develop an oral nanoplatform (CuO@SAG) possessing dual-pH/HS-responsive release characteristics. Importantly, CuO@SAG exhibited enrichment at the colonic inflammation site and relieved the inflammatory index, containing the recovery of colon length, spleen index, liver index, and body weight, as well as inflammatory cell infiltration. In vivo and in vitro experiments revealed the dual ROS and HS scavenging capacities of the nanoplatform. Additionally, CuO@SAG regulated tight junctions, mucus layers, and gut microbiota, which was accompanied by the downregulation of inflammatory cytokines. Notably, CuO@SAG also had excellent biocompatibility. In conclusion, this oral multiple-scavenging nanozyme platform provides a new and safe paradigm for the development of nanozymes for colitis treatment.
炎症性肠病在炎症部位涉及过量的活性氧（ROS）和硫化氢（HS）。纳米酶介导的ROS和HS清除疗法在结肠炎治疗方面具有前景。在此，我们合成了一种具有多种ROS清除能力的氧化铜纳米颗粒，并首次探索了其HS清除能力。用α-硫辛酸修饰的壳寡糖包覆在纳米颗粒上，以进一步增强HS清除能力。此外，在表面包覆海藻酸钙以构建具有双pH/HS响应释放特性的口服纳米平台（CuO@SAG）。重要的是，CuO@SAG在结肠炎症部位富集并减轻了炎症指标，包括结肠长度、脾脏指数、肝脏指数和体重的恢复以及炎症细胞浸润。体内和体外实验揭示了该纳米平台具有双重ROS和HS清除能力。此外，CuO@SAG调节紧密连接、黏液层和肠道微生物群，同时伴有炎症细胞因子的下调。值得注意的是，CuO@SAG还具有优异的生物相容性。总之，这种口服多清除纳米酶平台为开发用于结肠炎治疗的纳米酶提供了一种新的、安全的范例。
