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近红外调控纳米平台利用类过氧化物酶和类氧化酶活性的光热促进作用实现高效抗菌和抗生物膜治疗。

Near-Infrared-Controlled Nanoplatform Exploiting Photothermal Promotion of Peroxidase-like and OXD-like Activities for Potent Antibacterial and Anti-biofilm Therapies.

机构信息

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Hefei National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei 230027, China.

出版信息

ACS Appl Mater Interfaces. 2020 Nov 11;12(45):50260-50274. doi: 10.1021/acsami.0c14451. Epub 2020 Oct 27.

DOI:10.1021/acsami.0c14451
PMID:33108154
Abstract

Nanozymes that mimic peroxidase (POD) activity can convert HO into bactericidal free radicals, which is referred to as chemodynamic therapy (CDT). High glutathione (GSH) levels in the infectious tissue severely limit the performance of CDT. Herein, we report a near-infrared-controlled antibacterial nanoplatform that is based on encapsulating tungsten sulfide quantum dots (WSQDs) and the antibiotic vancomycin in a thermal-sensitive liposome. The system exploits the photothermal sensitivity of the WSQDs to achieve selective liposome rupture for the targeted drug delivery. We determined that WSQDs show a strong POD-like activity under physiological conditions and the oxidase-like activity, which can oxidate GSH to further improve the CDT efficacy. Moreover, we found that increased temperature promotes multiple enzyme-mimicking activities of WSQDs. This platform exerts antibacterial effects against Gram-positive Mu50 (a vancomycin-intermediate reference strain) and Gram-negative and disrupts biofilms for improved penetration of therapeutic agents inside biofilms. studies with mice bearing Mu50-caused skin abscess revealed that this platform confers potent antibacterial activity without obvious toxicity. Accordingly, our work illustrates that the photothermal and nanozyme properties of WSQDs can be deployed alongside a conventional therapeutic to achieve synergistic chemodynamic/photothermal/pharmaco therapy for powerful antibacterial effects.

摘要

模拟过氧化物酶 (POD) 活性的纳米酶可以将 HO 转化为杀菌自由基,这被称为化学动力学疗法 (CDT)。感染组织中高浓度的谷胱甘肽 (GSH) 严重限制了 CDT 的性能。在此,我们报告了一种基于近红外控制的抗菌纳米平台,该平台将硫化钨量子点 (WSQDs) 和抗生素万古霉素封装在热敏脂质体中。该系统利用 WSQDs 的光热敏感性实现了靶向药物递送的选择性脂质体破裂。我们确定 WSQDs 在生理条件下表现出强烈的 POD 样活性和氧化酶样活性,可以将 GSH 氧化进一步提高 CDT 效果。此外,我们发现升高的温度促进了 WSQDs 的多种酶模拟活性。该平台对革兰氏阳性 Mu50(万古霉素中介参考菌株)和革兰氏阴性菌表现出抗菌作用,并破坏生物膜以提高治疗剂在生物膜内的渗透。用 Mu50 引起的皮肤脓肿小鼠进行的研究表明,该平台具有强大的抗菌活性而没有明显的毒性。因此,我们的工作表明,WSQDs 的光热和纳米酶特性可以与传统治疗方法结合使用,以实现协同的化学动力学/光热/药物治疗,从而产生强大的抗菌效果。

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