α-Fe 2 O 3 based nanotherapeutics for near-infrared/dihydroartemisinin dual-augmented chemodynamic antibacterial therapy

• Published in: Acta biomaterialia Vol. 150; p. 367
• Main Authors: Xu, Yueying, Xiao, Le, Chen, Jia, Wu, Quanxin, Yu, Wenhua, Zeng, Weishen, Shi, Yaxin, Lu, Yingnian, Liu, Yun
• Format: Journal Article
• Language: English
• Published: England 15.09.2022
• Subjects: Anti-Bacterial Agents - pharmacology; Artemisinins; Cell Line, Tumor; Ferric Compounds; Ferrous Compounds; Hydrogen Peroxide - pharmacology; Nanoparticles - therapeutic use; Peroxidases; Tannins - pharmacology; Dihydroartemisinin; Photothermal effect; Chemodynamic therapy; α-FeO nanorods; Antibacterial therapy
• ISSN: 1878-7568

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 H O 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-Fe O nanorods with metal-polyphenol networks (MPN) led to the generation of an antibacterial nanoagent Fe O @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 H O level at the mildly acidic inflammatory microenvironment. To address these issues, we have developed a pH-responsive nanoagent (Fe O @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 H O 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.