Use of Cerium Oxide Nanoparticles Conjugated with MicroRNA-146a to Correct the Diabetic Wound Healing Impairment.
Use of Cerium Oxide Nanoparticles Conjugated with MicroRNA-146a to Correct the Diabetic Wound Healing Impairment.
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DOI：
10.1016/j.jamcollsurg.2018.09.017
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发表时间：
2019-01
影响因子：
5.2
通讯作者：
Liechty KW
中科院分区：
文献类型：
--
作者：
Zgheib C;Hilton SA;Dewberry LC;Hodges MM;Ghatak S;Xu J;Singh S;Roy S;Sen CK;Seal S;Liechty KW
糖尿病创面已成为21世纪最具挑战性的公共卫生问题之一，但目前还没有有效的治疗方法。我们先前已经证明，糖尿病伤口愈合障碍与炎症增加和调节microRNA miR-146a表达减少有关。我们已经将miR-146a连接到氧化铈纳米颗粒(CNP-miR146a)上，以靶向活性氧物种(ROS)和炎症。本研究旨在评价CNP-miR146a治疗糖尿病创面的疗效。在DB/DB小鼠背部皮肤上造成8毫米的创面，在损伤时用PBS或不同浓度的CNP-mir146a(1、10、100或1000 ng)处理。测量伤口闭合率，直至伤口完全愈合。愈合后4周，取哑铃形皮肤标本，中心为愈合创面，用Instron 5942测试装置测量最大载荷和最大弹性系数。我们的数据显示，用PBS或1 ng CNP-miR146a治疗的糖尿病伤口需要18天才能愈合。用10、100或1000 ng的CNP+miR-146a治疗可有效促进愈合，伤后第14天创面完全闭合。CNP-miR146a处理组愈合皮肤的生物力学性能有改善的趋势(最大载荷和弹性模量增加)，但未达到显著水平。我们发现100 ng剂量的CNP-miR146a促进了糖尿病伤口的愈合，并且不会损害愈合后皮肤的生物力学特性。这种基于纳米技术的疗法前景看好，未来的研究将保证将这种疗法转化为临床应用。(J am Coll Surg 2019；228：107-115。2018年由美国外科医生学会主办。由Elsevier Inc.出版。保留所有权利。)
Diabetic wounds have become one of the most challenging public health issues of the 21st century, yet there is no effective treatment available. We have previously shown that the diabetic wound healing impairment is associated with increased inflammation and decreased expression of the regulatory microRNA miR-146a. We have conjugated miR-146a to cerium oxide nanoparticles (CNP-miR146a) to target reactive oxygen species (ROS) and inflammation. This study aimed to evaluate the consequences of CNP-miR146a treatment of diabetic wounds. Eight-millimeter wounds were created on the dorsal skin of Db/Db mice and treated with PBS or differing concentrations of CNP-mir146a (1; 10; 100; or 1,000 ng) at the time of wounding. Rate of wound closure was measured until the wounds were fully healed. At 4 weeks post-healing, a dumbbell-shaped skin sample was collected, with the healed wound in the center, and an Instron 5942 testing unit was used to measure the maximum load and modulus. Our data showed that diabetic wounds treated with PBS or 1 ng CNP-miR146a took 18 days to heal. Treatment with 10, 100, or 1,000 ng of CNP+miR-146a effectively enhanced healing, and wounds were fully closed at day 14 post-wounding. The healed skin from the CNP-miR146a-treated group showed a trend of improved biomechanical properties (increased maximum load and modulus), however it did not reach significance. We found that a 100-ng dose of CNP-miR146a improved diabetic wound healing and did not impair the biomechanical properties of the skin post-healing. This nanotechnology-based therapy is promising, and future studies are warranted to transfer this therapy to clinical application. (J Am Coll Surg 2019;228:107–115. 2018 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.)
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影响因子：
14
作者：
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