Yujie Liu, Li Ma, Guodong Fang, Tan Li, Hongran Zhao, Ting Wu, Jiajia Zhang, Xia Qi, Xiangyue Hu, Hongwei Wang, Chao Yang, Depeng Shi
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引用次数: 0
Abstract
Rationale: Fungal keratitis remains clinically challenging due to limited drug bioavailability, frequent dosing, reactive oxygen species (ROS)-mediated stromal damage, perforation risk, and bacterial coinfection. In the study, we developed a feedback-regulated multifunctional corneal micropatch (MFCP) via 3D printing for the treatment of fungal keratitis.
Methods: The dual-network hydrogel micropatch comprises an ROS-responsive hydrogel (RRH), voriconazole-loaded F127DA micelles (VCZ-F127DA), and gatifloxacin-loaded cerium metal-organic frameworks (GAT-MOFs). We characterized its physicochemical properties and evaluated its biocompatibility, corneal healing capacity, ROS scavenging activity, and antimicrobial performance. Histological staining, cytokine assays, and transcriptomic sequencing were used to assess its therapeutic efficacy in a mouse model of fungal keratitis.
Results: MFCP exhibits tunable curvature, high transparency, and mechanical properties matching those of the cornea, along with good biocompatibility. High ROS level can accelerate breakdown of the micropatch and promote drug release, generating strong synergistic antifungal and antibacterial activities. The released GAT-MOFs scavenge excessive ROS, forming a negative feedback loop. In the mouse model of fungal keratitis, MFCP mitigates corneal infection, lowers proinflammatory cytokines, and accelerates tissue repair, with therapeutic efficacy superior to that of voriconazole eye drops. Transcriptomic analysis reveals suppression of NF-κB-mediated inflammatory signaling and upregulation of corneal regenerative pathways after treatment with MFCP.
Conclusion: These findings demonstrate that MFCP represents a viable therapeutic option for fungal keratitis.
期刊介绍：
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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