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CuS nanoenzyme against bacterial infection by in situ hydroxyl radical generation on bacteria surface

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Abstract

Nanoenzyme-mediated antibacterial strategies have been widely exploited to overcome the shortcomings (such as drug resistance and mild-to-severe side effects) of antibiotic therapy. The peroxidase-like activity of nanoenzymes possesses great potential against bacterial infection by the generation of hydroxyl radical (·OH) in the specific microenvironment. However, the lifetime of ·OH is extremely short, and a large amount of the ·OH generated within the infection microenvironment cannot come into contact with bacteria quickly enough, thus resulting in low treatment efficiency. Here, chitosan-oligosaccharide-modified CuS nanoparticles possessing positive charges (PCuS NPs) were prepared using a one-pot method. PCuS NPs exhibited efficient peroxidase-like activity. Importantly, the PCuS NPs can combine with bacteria via electrostatic attraction. The direct contact between the PCuS NPs and bacteria enabled the generation of ·OH in situ on the bacterial surface, ultimately leading to a high antibacterial efficacy at a low concentration in the presence of H2O2. At an effective antibacterial concentration, the PCuS NPs exhibited high cytocompatibility. Furthermore, in vivo results revealed that PCuS NPs not only decreased the size of abscesses but also reduced inflammation and promoted collagen fiber formation. Therefore, PCuS NPs possess great potential against bacterial infection via in situ ·OH generation based on electrostatic attraction.

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摘要

为了克服抗生素治疗中存在的耐药性和中度至重度副作用等弊端，纳米酶介导的抗菌策略得到广泛的应用。通过 在特定微环境中产生羟基自由基（·OH），具有类过氧化物酶活性的纳米酶在治疗细菌感染中具有巨大的潜力。 然而，·OH 的寿命非常短，导致在微环境中产生的大量·OH 无法足够快速地接触细菌，因此治疗效率偏低。在本 研究中，通过一步法制备了带正电荷的壳寡糖修饰的CuS 纳米颗粒（PCuS NPs）。PCuS NPs 具有高效的类过氧 化物酶活性。重要的是，PCuS NPs 能够通过静电吸引与细菌结合。PCuS NPs 和细菌的直接接触能够使·OH 在细 菌表面原位产生，最终在低浓度H2O2 存在下呈现高的抗菌效率。在有效抗菌浓度下，PCuS NPs 具有良好的细胞 相容性。此外，体内结果表明，PCuS NPs 不仅能减小脓肿的尺寸，而且还能减轻炎症并促进胶原纤维的形成。综 上所述，PCuS NPs 能够通过静电吸引在细菌表面原位生成·OH，具有高的抗细菌感染的应用潜力。

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (No. 82100974), the Natural Science Foundation of Shandong Province (No. ZR2021QH241), and Qilu Young Scholars Program of Shandong University.

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  1. Zhao Li and Cheng-Jia Xie have contributed equally to this work.

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  1. Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012, China

    Zhao Li, Cheng-Jia Xie, Qun Zhang & Bao-Jin Ma

  2. Jinan Food and Drug Inspection and Testing Center, Jinan, 250010, China

    Xiao-Wei Ren

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Li, Z., Xie, CJ., Ren, XW. et al. CuS nanoenzyme against bacterial infection by in situ hydroxyl radical generation on bacteria surface. Rare Met. 42, 1899–1911 (2023). https://doi.org/10.1007/s12598-022-02223-7

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