NIR-activated multi-hit therapeutic Ag₂S quantum dot-based hydrogel for healing of bacteria-infected wounds

Hydrogel dressings are highly biocompatible and can maintain a moist wound environment, suggesting constructing an efficient multi-modal antibacterial hydrogel platform is a promising strategy for treating bacterial wound infections. In this work, a composite Ag₂S quantum dot/mSiO₂ NPs hydrogel (NP hydrogel) with antibacterial ability was constructed by incorporating Ag₂S quantum dots (QDs) modified by mesoporous silica (mSiO₂) into the network structure of 3-(trimethoxylmethosilyl) propyl methacrylate based on free radical polymerization. The NP hydrogel showed outstanding controllable photothermal and photodynamic characteristics under 808 nm near infrared (NIR) light irradiation, with a photothermal conversion efficiency of 57.3%. Additionally, the release of Ag⁺ could be controlled by the inherent volume change of the NP hydrogel made of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) during NIR laser exposure, with the embedded Ag₂S QDs working as a reservoir to release Ag⁺ continuously from the hydrogel matrix to achieve bactericidal activity. The synergetic effects between hyperthermia, radical oxygen species, and Ag⁺ released under NIR radiation endowed the NP hydrogel with prominent antibacterial properties against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), with an inhibition rate of 99.7% and 99.8%, respectively. In vivo wound healing experiments indicated that the NP hydrogel could enhance bacterial clearance, increase collagen coverage area and up-regulate VEGF expression, exhibiting high biocompatibility. Overall, this study proposed an efficient and highly biocompatible multi-modal therapeutic nanohydrogel, opening up a new way for developing broad-spectrum antibacterial wound dressings to treat bacterial wound infections. STATEMENT OF SIGNIFICANCE: Bacterial wound infection is still one of the most difficult medical problems. In this work, a stimulating NIR-responsive hydrogel encapsulating functional Ag₂S QDs was prepared, which showed high photothermal conversion efficiency (57.3%) and outstanding antibacterial ability under 808 nm NIR laser, killing 99.7% and 99.8% of E. coli and MRSA in 4 min, respectively. During NIR light irradiation, the release rate of Ag⁺ could be regulated by the intrinsic volume transition of the hydrogel, leading to remarkable antibacterial properties in vitro and in vivo under the combined action of hyperthermia, radical oxygen species and Ag⁺ released. This study proposed a novel multi-modal therapeutic nanohydrogel, opening up a new way for developing broad-spectrum antibacterial wound dressings to treat bacterial wound infections.