Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, China.
Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, China.
Acta Biomater. 2022 Sep 15;150:367-379. doi: 10.1016/j.actbio.2022.07.047. Epub 2022 Jul 30.
Due to the negligible bacterial resistance, chemodynamic therapy (CDT) is a promising treatment for bacterial infection. However, it is severely impeded by the constant body temperature, shortage of Fe(Ⅱ) ions and insufficient HO level in infected tissue. To enhance the therapeutic efficiency of CDT, improved strategies are urgently needed to tackle these problems. Herein, we exploited an infection microenvironment-responsive nanotherapeutics for near-infrared (NIR)/dihydroartemisinin (DHA) dual-augmented antibacterial CDT. The convenient encapsulation of DHA-loaded α-FeO nanorods with metal-polyphenol networks (MPN) led to the generation of an antibacterial nanoagent FeO@DHA@MPN (FDM). Afterwards, its photothermal and peroxidase-like activities were intensively studied. Furthermore, the bactericidal efficacy of FDM was evaluated through both in vitro and in vivo antibacterial assays. Firstly, FDM showed both satisfactory photothermal and NIR/DHA dual-augmented peroxidase-like activities. Besides, it exhibited a pH-responsive release behavior of both Fe(Ⅱ) ions and DHA. Moreover, it presented tannic acid-mediated bacterial adhesion effect. In vitro experiments demonstrated that FDM could achieve a satisfactory efficiency against both planktonic bacteria and biofilms. In vivo assays illustrated both the extraordinary synergistic antibacterial effect and efficient anti-inflammatory ability of FDM. The outcomes indicated that the exploited antibacterial agent could offer new insight on developing intelligent nanotherapeutics for clinical use in the future. STATEMENT OF SIGNIFICANCE: The antibacterial efficiency of chemodynamic therapy (CDT) is seriously limited by the constant body temperature, shortage of Fe(Ⅱ) ions and insufficient HO level at the mildly acidic inflammatory microenvironment. To address these issues, we have developed a pH-responsive nanoagent (FeO@DHA@MPN) for near-infrared (NIR)/dihydroartemisinin (DHA) dual-augmented CDT. Through the NIR-induced photothermal effect of exterior Fe(Ⅲ)/tannic acid complex, the increased local temperature led to a photothermal enhanced CDT. Besides, a continuous supply of Fe(Ⅱ) ions could be achieved by tannic acid-mediated Fe(Ⅲ) reduction. Moreover, DHA was adopted as a substitute for HO to initiate DHA-mediated CDT. Both in vitro and in vivo assays demonstrated its outstanding bactericidal efficiency. Therefore, the developed nanotherapeutics could be a promising candidate for clinical trials.
由于细菌耐药性可以忽略不计，化学动力学疗法（CDT）是治疗细菌感染的一种很有前途的方法。然而，它受到恒定体温、感染组织中缺乏 Fe（Ⅱ）离子和不足的 HO 水平的严重阻碍。为了提高 CDT 的治疗效果，迫切需要改进策略来解决这些问题。在此，我们利用感染微环境响应性纳米治疗剂，实现了近红外（NIR）/二氢青蒿素（DHA）双重增强的抗菌 CDT。DHA 负载的α-FeO 纳米棒与金属多酚网络（MPN）的方便封装导致了抗菌纳米制剂 FeO@DHA@MPN（FDM）的生成。随后，我们深入研究了其光热和过氧化物酶样活性。此外，通过体外和体内抗菌试验评估了 FDM 的杀菌效果。首先，FDM 表现出令人满意的光热和 NIR/DHA 双重增强的过氧化物酶样活性。此外，它还表现出 Fe（Ⅱ）离子和 DHA 的 pH 响应释放行为。此外，它还表现出单宁酸介导的细菌粘附作用。体外实验表明，FDM 可以对浮游菌和生物膜实现令人满意的效率。体内实验表明，FDM 具有非凡的协同抗菌作用和有效的抗炎能力。结果表明，所开发的抗菌剂可以为未来临床应用的智能纳米治疗剂的开发提供新的见解。
