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用于治疗深部皮肤真菌感染且无耐药性的基于透明质酸的硫化铜纳米酶可生物降解微针

Hyaluronic Acid-Based CuS Nanoenzyme Biodegradable Microneedles for Treating Deep Cutaneous Fungal Infection without Drug Resistance.

作者信息

Wang Bingjie, Zhang Wenshang, Pan Qi, Tao Jiaojiao, Li Shuang, Jiang Tianze, Zhao Xia

机构信息

Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

The Affiliated Qingdao Central Hospital of Qingdao University, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao 266042, China.

出版信息

Nano Lett. 2023 Feb 22;23(4):1327-1336. doi: 10.1021/acs.nanolett.2c04539. Epub 2023 Feb 7.

DOI:10.1021/acs.nanolett.2c04539
PMID:36749122
Abstract

Deep cutaneous fungal infection (DCFI) is difficult to be treated by the traditional topical application due to low drug transdermal efficiency, poor fungicidal effect, and easy to develop drug resistance. Here, we report a novel biodegradable microneedle patch (CuS/PAF-26 MN) for DCFI treatment. CuS/PAF-26 MN is composed of hyaluronic acid (HA) and sodium carboxymethylcellulose (CMC-Na), which can simultaneously deliver copper sulfide nanoenzyme (CuS NE) and antimicrobial peptide (PAF-26). CuS NE catalyzes hydrogen peroxide to produce reactive oxygen species (ROS), and PAF-26 directly destroys the cell membrane of fungi. The combination of ROS toxicity produced by CuS NE and the destruction of fungal membrane by PAF-26 shows strong antifungal activities without drug resistance. The antifungal effect of CuS/PAF-26 MN is significantly superior to that of traditional ointment, CuS MN or PAF-26 MN in a DCFI mouse model. Therefore, CuS/PAF-26 MN shows a promising application prospect for treating DCFI.

摘要

深部皮肤真菌感染(DCFI)由于药物透皮效率低、杀菌效果差且易产生耐药性,难以通过传统的局部用药进行治疗。在此,我们报道了一种用于治疗DCFI的新型可生物降解微针贴片(CuS/PAF-26 MN)。CuS/PAF-26 MN由透明质酸(HA)和羧甲基纤维素钠(CMC-Na)组成,可同时递送硫化铜纳米酶(CuS NE)和抗菌肽(PAF-26)。CuS NE催化过氧化氢产生活性氧(ROS),PAF-26直接破坏真菌细胞膜。CuS NE产生的ROS毒性与PAF-26对真菌膜的破坏相结合,显示出强大的抗真菌活性且无耐药性。在DCFI小鼠模型中,CuS/PAF-26 MN的抗真菌效果明显优于传统软膏、CuS MN或PAF-26 MN。因此,CuS/PAF-26 MN在治疗DCFI方面显示出有前景的应用前景。

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