Abstract：
Renal ischemia-reperfusion injury (IRI) is a major contributing factor to the development of acute kidney injury (AKI) and has resulted in considerable morbidity and mortality. Persistent inflammatory responses and excessive reactive oxygen species (ROS) in the kidney following IRI can severely delay tissue repair, making it challenging to effectively promote IRI regeneration. Herein, we report an approach to enhance immunotherapy using interleukin-10 (IL-10) to promote IRI regeneration by loading IL-10 onto rectangular DNA origami nanostructures (rDON). rDON can significantly enhance the renal accumulation and retention time of IL-10, enabling it to effectively polarize type 1 macrophages into type 2 macrophages, thereby significantly reducing proinflammatory factors and increasing anti-inflammatory factors. In addition, DNA origami helps mitigate the harmful effects of ROS during renal IRI. The administration of IL-10-loaded DNA origami effectively improves kidney function, resulting in a notable reduction in blood urea nitrogen, serum uric acid, and serum creatinine levels. Our study demonstrates that the integration of anti-inflammatory cytokines within DNA origami holds promise as a strategic approach for cytokine immunotherapy in patients with AKI and other renal disorders.
摘要：
肾缺血再灌注损伤（IRI）是急性肾损伤（AKI）发展的主要因素，并已导致相当高的发病率和死亡率。IRI后肾脏持续的炎症反应和过度的活性氧（ROS）可严重延迟组织修复，有效促进IRI再生具有挑战性。在这里，我们报道了一种使用白细胞介素-10(IL-10)增强免疫治疗的方法,通过将IL-10加载到矩形DNA折纸纳米结构(rDON)上来促进IRI再生.rDON可以显著增强IL-10的肾脏积累和保留时间，使其能够有效地将1型巨噬细胞极化为2型巨噬细胞，从而显著降低促炎因子,增加抗炎因子。此外,DNA折纸有助于减轻肾IRI期间ROS的有害影响。装载IL-10的DNA折纸的给药有效地改善了肾功能，导致血尿素氮显著减少，血清尿酸，和血清肌酐水平.我们的研究表明，在DNA折纸中整合抗炎细胞因子有望成为AKI和其他肾脏疾病患者细胞因子免疫治疗的战略方法。
