Wang Chi-Pin James, Ko Ga Ryang, Lee Yun Young, Park Juwon, Park Wooram, Park Tae-Eun, Jin Yoonhee, Kim Se-Na, Lee Jung Seung, Park Chun Gwon
Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), Suwon, Gyeonggi, 16419, Republic of Korea.
Department of Intelligent Precision Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), Suwon, Gyeonggi, 16419, Republic of Korea.
Nano Converg. 2024 Feb 8;11(1):6. doi: 10.1186/s40580-024-00414-9.
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a family of chronic disorders along the gastrointestinal tract. Because of its idiopathic nature, IBD does not have a fundamental cure; current available therapies for IBD are limited to prolonged doses of immunomodulatory agents. While these treatments may reduce inflammation, limited therapeutic efficacy, inconsistency across patients, and adverse side effects from aggressive medications remain as major drawbacks. Recently, excessive production and accumulation of neutrophil extracellular traps (NETs) also known as NETosis have been identified to exacerbate inflammatory responses and induce further tissue damage in IBD. Such discovery invited many researchers to investigate NETs as a potential therapeutic target. DNase-I is a natural agent that can effectively destroy NETs and, therefore, potentially reduce NETs-induced inflammations even without the use of aggressive drugs. However, low stability and rapid clearance of DNase-I remain as major limitations for further therapeutic applications. In this research, polymeric nanozymes were fabricated to increase the delivery and therapeutic efficacy of DNase-I. DNase-I was immobilized on the surface of polymeric nanoparticles to maintain its enzymatic properties while extending its activity in the colon. Delivery of DNase-I using this platform allowed enhanced stability and prolonged activity of DNase-I with minimal toxicity. When administered to animal models of IBD, DNase-I nanozymes successfully alleviated various pathophysiological symptoms of IBD. More importantly, DNase-I nanozyme administration successfully attenuated neutrophil infiltration and NETosis in the colon compared to free DNase-I or mesalamine.
炎症性肠病（IBD），包括克罗恩病和溃疡性结肠炎，是一类沿胃肠道的慢性疾病。由于其特发性本质，IBD尚无根本治愈方法；目前可用的IBD治疗方法仅限于长期使用免疫调节药物。虽然这些治疗可能会减轻炎症，但治疗效果有限、患者间疗效不一致以及强效药物的副作用仍然是主要缺点。最近，已发现中性粒细胞胞外诱捕网（NETs）（也称为NETosis）的过度产生和积累会加剧炎症反应并在IBD中导致进一步的组织损伤。这一发现促使许多研究人员将NETs作为潜在的治疗靶点进行研究。脱氧核糖核酸酶I（DNase-I）是一种天然物质，能够有效破坏NETs，因此，即使不使用强效药物也有可能减轻NETs诱导的炎症。然而，DNase-I的低稳定性和快速清除率仍然是其进一步治疗应用的主要限制。在本研究中，制备了聚合物纳米酶以提高DNase-I的递送效率和治疗效果。将DNase-I固定在聚合物纳米颗粒表面，以保持其酶活性，同时延长其在结肠中的活性。使用该平台递送DNase-I可提高其稳定性并延长其活性，且毒性最小。将DNase-I纳米酶给予IBD动物模型时，成功减轻了IBD的各种病理生理症状。更重要的是，与游离DNase-I或美沙拉嗪相比，给予DNase-I纳米酶成功减轻了结肠中的中性粒细胞浸润和NETosis。
