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具有双酶级联反应活性的自组装血红素-肝素用于急性肾损伤。

Self-assembled hemin-conjugated heparin with dual-enzymatic cascade reaction activities for acute kidney injury.

机构信息

School of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.

School of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.

出版信息

Carbohydr Polym. 2023 Sep 15;316:121088. doi: 10.1016/j.carbpol.2023.121088. Epub 2023 Jun 2.


DOI:10.1016/j.carbpol.2023.121088
PMID:37321716
Abstract

Nanozymes have prominent catalytic activities with high stability as a substitute for unstable and expensive natural enzymes. However, most nanozymes are metal/inorganic nanomaterials, facing difficulty in clinical translation due to their unproven biosafety and limited biodegradability issues. Hemin, an organometallic porphyrin, was newly found to possess superoxide dismutase (SOD) mimetic activity along with previously known catalase (CAT) mimetic activity. However, hemin has poor bioavailability due to its low water solubility. Therefore, a highly biocompatible and biodegradable organic-based nanozyme system with SOD/CAT mimetic cascade reaction activity was developed by conjugating hemin to heparin (HepH) or chitosan (CS-H). Between them, Hep-H formed a smaller (<50 nm) and more stable self-assembled nanostructure and even possessed much higher and more stable SOD and CAT activities as well as the cascade reaction activity compared to CS-H and free hemin. Hep-H also showed a better cell protection effect against reactive oxygen species (ROS) compared to CS-H and hemin in vitro. Furthermore, Hep-H was selectively delivered to the injured kidney upon intravenous administration at the analysis time point (24 h) and exhibited excellent therapeutic effects on an acute kidney injury model by efficiently removing ROS, reducing inflammation, and minimizing structural and functional damage to the kidney.

摘要

纳米酶具有突出的催化活性和高稳定性,可作为不稳定且昂贵的天然酶的替代品。然而,大多数纳米酶是金属/无机纳米材料,由于其生物安全性尚未得到证实和有限的生物降解性问题,在临床转化上面临困难。血红素是一种金属有机卟啉,最近被发现具有超氧化物歧化酶(SOD)模拟活性,同时具有先前已知的过氧化氢酶(CAT)模拟活性。然而,由于其低水溶性,血红素的生物利用度较差。因此,通过将血红素与肝素(HepH)或壳聚糖(CS-H)缀合,开发了一种具有 SOD/CAT 模拟级联反应活性的高度生物相容性和可生物降解的有机纳米酶系统。在它们之间,Hep-H 形成更小(<50nm)且更稳定的自组装纳米结构,甚至具有更高且更稳定的 SOD 和 CAT 活性以及级联反应活性,与 CS-H 和游离血红素相比。Hep-H 还显示出比 CS-H 和血红素更好的体外细胞保护作用,以抵抗活性氧(ROS)。此外,在静脉给药后,Hep-H 可选择性递送至受损的肾脏,并且通过有效清除 ROS、减轻炎症以及最小化对肾脏的结构和功能损伤,在急性肾损伤模型中表现出优异的治疗效果。

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引用本文的文献

[1]
Targeted co-delivery of IL-10 and catalase for cooperative therapeutic effect on acute kidney injury.

Bioact Mater. 2025-6-19

[2]
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[3]
Nanotechnology-Based Drug Delivery Systems for Treating Acute Kidney Injury.

ACS Biomater Sci Eng. 2024-10-14

[4]
Non-Anticoagulant Activities of Low Molecular Weight Heparins-A Review.

Pharmaceuticals (Basel). 2023-9-5

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