Jung Junyoung, Kwon Kiyoon, Tae Giyoong
Department of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Republic of Korea.
Bioact Mater. 2025 Jun 19;52:604-622. doi: 10.1016/j.bioactmat.2025.06.020. eCollection 2025 Oct.
Kidney disease has emerged as a significant public health concern, affecting approximately 10 % of adults worldwide. Especially, acute kidney injury (AKI) increases in-hospital morbidity and mortality. This study introduces a dual-therapeutic strategy combining interleukin-10 (IL-10), an anti-inflammatory cytokine, and catalase (CAT), a reactive oxygen species (ROS)-scavenging enzyme, for the treatment of inflammatory kidney injury. A kidney-targeting peptide-conjugated, Pluronic-based nanocarrier (K-NC) was developed to enable the co-delivery and sustained release of IL-10 and CAT. Compared to no-ligand conjugated NC, K-NC was selectively accumulated in the damaged kidneys while reducing liver accumulation, CAT effectively reduced ROS levels in tubular epithelial cells, while IL-10 suppressed inflammatory cytokine expression and promoted M2 macrophage polarization, co-delivery of IL-10 and CAT using K-NC resulted in significantly enhanced therapeutic effects on AKI compared to single delivery of IL-10 or CAT using K-NC (IL-10@K-NC or CAT@K-NC), or co-delivery of IL-10 and CAT using no-ligand conjugated NC (IL-10/CAT@NC) by showing reduced levels of serum creatinine and BUN, reduced reactive oxygen species, reduced pro-inflammatory cytokine expression, inhibited M1 macrophage polarization, and promoted M2 macrophage polarization in the kidney. This study not only presents a promising approach for the treatment of kidney inflammation but is also the first report demonstrating enhanced therapeutic effects through a combination of an antioxidant enzyme with an anti-inflammatory cytokine.
肾脏疾病已成为一个重大的公共卫生问题，影响着全球约10%的成年人。特别是，急性肾损伤（AKI）会增加住院患者的发病率和死亡率。本研究引入了一种双重治疗策略，即将抗炎细胞因子白细胞介素-10（IL-10）和活性氧（ROS）清除酶过氧化氢酶（CAT）联合用于治疗炎性肾损伤。开发了一种基于普朗尼克的、与肾脏靶向肽偶联的纳米载体（K-NC），以实现IL-10和CAT的共递送和持续释放。与未偶联配体的纳米载体相比，K-NC在受损肾脏中选择性蓄积，同时减少了肝脏蓄积，CAT有效降低了肾小管上皮细胞中的ROS水平，而IL-10抑制了炎性细胞因子的表达并促进了M2巨噬细胞极化，与使用K-NC单独递送IL-10或CAT（IL-10@K-NC或CAT@K-NC），或使用未偶联配体的纳米载体共递送IL-10和CAT（IL-10/CAT@NC）相比，使用K-NC共递送IL-10和CAT对AKI产生了显著增强的治疗效果，表现为血清肌酐和尿素氮水平降低、活性氧减少、促炎细胞因子表达降低、肾脏中M1巨噬细胞极化受到抑制以及M2巨噬细胞极化得到促进。本研究不仅提出了一种治疗肾脏炎症的有前景的方法，也是首次报道通过抗氧化酶与抗炎细胞因子联合使用来增强治疗效果。
