Kidney-Targeted Nanoparticles Loaded with the Natural Antioxidant Rosmarinic Acid for Acute Kidney Injury Treatment,Small

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Kidney-Targeted Nanoparticles Loaded with the Natural Antioxidant Rosmarinic Acid for Acute Kidney Injury Treatment
Small ( IF 13.0 ) Pub Date : 2022-10-17 , DOI: 10.1002/smll.202204388
Jiajia Li _{1,

2} , Qijia Duan ₃ , Xiaona Wei _{1,

2} , Jianping Wu _{1,

2} , Qiongqiong Yang _{1,

2}

Affiliation

Acute kidney injury (AKI) is a common clinical disease with high morbidity and mortality, and with a lack of effective drugs for treatment. Oxidative stress is very important in the occurrence and progression of AKI, and antioxidants use is one of the promising treatments. Rosmarinic acid (RA) is a ubiquitous natural polyphenol with powerful antioxidant and anti-inflammatory activities. Due to its inherent characteristic with poor water solubility and inferior bioavailability, its clinical application is impeded. Hence, the authors design a nanoparticle for effectively delivering RA, which is a chemical complex of RA and fourth-generation poly-amidoamine-based amphiphilic polymer (G4-PAMAM). The nanoparticle is modified with l-serine due to the specific interaction between kidney injury molecule–1 (Kim-1) and serine, which eventually generates a promising AKI kidney–targeting nanoparticle (S-G-R). The S-G-R is rapidly cumulated and long-term retained in ischemia-reperfusion–induced AKI kidneys, especially in the damaged renal tubular cells. The S-G-R exhibits more excellent antioxidative and antiapoptotic effects in vitro and has a more outstanding ability to improve the renal function, repair damaged renal tissue, and decrease oxidative stress, inflammatory response and apoptosis of tubular cells in vivo. Overall, this study might develop a safe and effective targeting strategy for the therapy of AKI.

中文翻译：

负载天然抗氧化剂迷迭香酸的肾脏靶向纳米颗粒用于治疗急性肾损伤

急性肾损伤（AKI）是临床常见疾病，发病率和死亡率较高，且缺乏有效的治疗药物。氧化应激在 AKI 的发生和进展中非常重要，抗氧化剂的使用是有前途的治疗方法之一。迷迭香酸（RA）是一种普遍存在的天然多酚，具有强大的抗氧化和抗炎活性。由于其固有的水溶性差、生物利用度差的特点，限制了其临床应用。因此，作者设计了一种有效递送 RA 的纳米颗粒，它是 RA 和第四代聚酰胺基胺基两亲聚合物 (G4-PAMAM) 的化学复合物。由于肾损伤分子-1 (Kim-1) 和丝氨酸之间的特异性相互作用，纳米颗粒被 L-丝氨酸修饰，最终产生了一种有前途的 AKI 肾脏靶向纳米颗粒 (SGR)。 SGR 在缺血再灌注诱导的 AKI 肾脏中迅速积累并长期保留，尤其是在受损的肾小管细胞中。 SGR在体外表现出更优异的抗氧化和抗凋亡作用，在体内具有更突出的改善肾功能、修复受损肾组织、减少肾小管细胞氧化应激、炎症反应和凋亡的能力。总体而言，这项研究可能会为 AKI 的治疗制定安全有效的靶向策略。

更新日期：2022-10-17

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