Enhanced Synergistic Photothermal–Chemotherapy in Bacterial Keratitis Treatment Using Halogen-Bonded Organic Frameworks (XOFs) Based on N⋯Br⁺⋯N Bonds

Abstract

The swift progression of bacterial keratitis necessitates expeditious therapeutic intervention. Present therapeutic methodologies are characterized by their protracted duration and invasiveness, which often result in suboptimal antibiotic therapy. Consequently, there is an imperative requirement for the development of novel therapeutic approaches for the management of bacterial keratitis. In this study, we present two types of XOFs connected by [N···Br⁺···N] interactions. These frameworks were characterized using ¹H NMR, IR, XPS, SAXS, and HR-TEM. Two-dimensional (2D) structural models were established based on PXRD data and theoretical simulations. The application of these XOFs as novel antibacterial agents for the treatment of bacterial keratitis were explored, and the effects of different connection knots and hydrophilicity on the antibacterial efficacy of XOFs were compared. As expected, the therapeutic effect of XOFs based on [N···Br⁺···N] interactions are superior to XOFs based on [N···I⁺···N] interactions. The therapeutic effect of TPPA-based XOFs with good hydrophilicity is better than TPPE-based XOFs. In addition, a photothermal agent (IR820) was loaded onto XOF(Br)-TPPA for combined photothermal and chemotherapy, with experimental results indicating a substantial enhancement in therapeutic efficacy. This work not only deepens our understanding of halogen-bonded organic frameworks but also paves the way for the application of XOFs in biomedical materials.

Keywords

antibacterial agent / bacterial keratitis / [N···Br⁺···N] halogen bond / supramolecular medicine / synergistic therapeutics

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2025 The Author(s). Aggregate published by SCUT, AIEI and John Wiley & Sons Australia, Ltd.