Multicomponent reaction-driven guanine-functionalized G-quadruplex hydrogel for targeted antimicrobial treatment of infected wounds

Abstract

Currently, the management of infected wounds is a significant challenge in healthcare due to the increasing prevalence of antibiotic-resistant bacteria and the complex nature of wound care. Bacterial wound infections cause serious health problems and place a heavy burden on both patients and healthcare systems. Therefore, there is an urgent need to develop new treatment strategies in healthcare, especially for the treatment of bacteria infected wound dressings. Hence, injectable hydrogels with inherent antimicrobial properties can serve as wound dressing materials that accelerate healing efficiency during skin infections. Herein, multicomponent self-assembly techniques have been employed to develop biomimetic low molecular weight G-quadruplex hydrogel at physiological condition. Guanosine (natural H-bonding molecule), 2-formylphenylboronic acid (dual functional anchor) and a valine derived open chain pseudopeptide (a bidentate anchor) are synergistically involved to generate the multicomponent self-assembled dynamic iminoboronate G-quadruplex hydrogel with inherent antibacterial and antifungal properties intended for treating wounds. The presence of bifunctional iminoboronate bonds makes the G-quadruplex hydrogel dynamic and responsive to stimuli. This multicomponent self-assembled injectable, thixotropic G-quadruplex hydrogel possesses excellent biocompatibility and exhibits inherent antimicrobial activity against a wide range of bacterial species. Furthermore, the hydrogel demonstrates excellent antifungal activity against the disease-prone fungal species Aspergillus niger and Penicillium spp. Notably, in-vivo studies on bacteria and fungus- infected rat model confirms that the proposed biocompatible G-quadruplex hydrogel can rapidly heal wounds by stopping bleeding, killing bacteria and fungus, and promoting collagen deposition, and epidermal regeneration at the wound site. Hence, this multifunctional stimulus responsive G-quadruplex hydrogel holds promising potential for preventing localized bacterial and fungal infections. Additionally, it could serve as an effective wound dressing material for treating wounds caused by bacterial infections. © 2025 Elsevier B.V., All rights reserved.