Multifunctional MoO3-X Nanozyme-Hydrogel for Synergistic Photothermal Antibacterial Therapy and Enhanced Healing of Wounds Infected with Drug‑Resistant Bacteria.
Aug 2026· ACS Applied Materials and Interfaces· 0 citations· 49 references
Medicine
TL;DR
This work demonstrates a safe and effective strategy for combating MDR infections through the combined action of photothermal therapy and nanozyme catalysis, offering promising potential for clinical wound management.
Abstract
Multidrug-resistant (MDR) bacterial infections and recalcitrant biofilms remain intractable barriers to wound healing, with traditional antibiotics offering limited efficacy due to resistance and poor biofilm penetration. To address this unmet clinical need, we innovatively engineered a multifunctional composite hydrogel (MoO3-X@CG-ODP) by integrating oxygen-vacancy-rich MoO3-X nanozymes into a dynamic cross-linking network formed by L-glutamine-grafted chitosan (CG) and 3-aminophenylboronic acid-mediated oxidized dextran (ODP). The composite exhibits a stacked nanosheet morphology (∼240 nm), a high photothermal conversion efficiency of 49.70%, and peroxidase-like activity. Under 808 nm near-infrared irradiation, the hydrogel achieves >99% inhibition against MDR Escherichia coli and Staphylococcus aureus, along with effective biofilm eradication. In a murine wound model, the material significantly accelerated wound closure, up-regulated vascular endothelial growth factor (VEGF), down-regulated tumor necrosis factor-α (TNF-α), and maintained excellent biosafety. This work demonstrates a safe and effective strategy for combating MDR infections through the combined action of photothermal therapy and nanozyme catalysis, offering promising potential for clinical wound management.
Bacterial infection impeded wound healing, causing significant discomfort and endangering the lives of patients. Overusing antibiotics to address such infections has spurred drug resistance in certain pathogenic bacteria. Hence, there is a pressing demand for a non-antibiotic-dependent versatile dressing to amplify on-site antibacterial efficacy, effectively averting wound infections, and fostering wound recovery. In this study, a pioneering near-infrared activated antibacterial EPLGA/OHADA@HMCuS hydrogel was formulated by doping hollow mesoporous copper sulfide (HMCuS) into the three-dimensional spatial network structure formed between gallic acid-modified ε-polylysine (EPL-GA) and dopamine-engineered and oxidized hyaluronic acid (OHADA). This hydrogel not only exhibited exceptional mechanical characteristics and tissue adhesion but also showcased favorable biocompatibility, sustaining cellular viability. The obtained EPLGA/OHADA@ HMCuS hydrogel not only demonstrated robust antibacterial activity against E. coli and S. aureus under laser irradiation but also exhibited a pronounced cell migration-promoting effect. In mouse models of tail amputation and liver injury, this hydrogel exhibited remarkable hemostatic capabilities and was also capable of substantially expediting wound healing in bacterial-infected wounds-bearing rats, as evidenced by its promotion of collagen deposition and angiogenesis, along with the downregulation of inflammatory factors. Hence, this multifunctional EPLGA/OHADA@HMCuS hydrogel stands out as a highly promising wound-assisting material, exhibiting broad potential for clinical application in the future management of infected wounds.
N. Wang, Wei Jiang, Feiyu Lu et al.· Biomaterials Advances· 0 citations
The refractory healing of diabetic wounds represents a major clinical challenge, primarily attributed to a vicious cycle formed by persistent bacterial infection, excessive oxidative stress, and a dysregulated immune microenvironment. To simultaneously address multiple pathological barriers, an intelligent composite nanoplatform was designed and constructed in this study, integrating near-infrared (NIR) photothermal therapy, reactive oxygen species (ROS) scavenging, antimicrobial activity, and immunomodulation. A mesoporous polydopamine (MPDA) core was loaded with chlorogenic acid (CGA), a natural antioxidant, and further coated with a copper-zinc bimetallic organic framework (Cu/Zn-MOF) to fabricate Cu/Zn-MOF@CGA@MPDA NPs, exhibiting pH-responsive dissociation in the acidic infected wound microenvironment. Under 808 nm near-infrared irradiation, the fabricated NPs showed excellent photothermal performance, efficiently eliminating bacteria and biofilms in vitro. They also scavenged ROS to relieve oxidative damage and promoted macrophage polarization from the pro-inflammatory M1 to pro-healing M2 phenotype. In a diabetic rat model of infected full-thickness skin wounds, the nanoplatform achieved antibacterial and anti-inflammatory effects simultaneously. Such synergistic functions promoted collagen deposition and re-epithelialization, thereby accelerating diabetic wound healing. Histological and hematological tests verified its good biocompatibility and biosafety. This work developed a synergistic single-platform strategy for precise regulation of diabetic wound microenvironments, providing a promising therapeutic alternative for refractory diabetic wound treatment.
Infected burn wounds are characterized by bacterial invasion, oxidative stress, and persistent inflammation, which severely impair tissue regeneration. Herein, we report a crosslinker-free, hydrogen-bonded cationic guar gum hydrogel (CBBM) co-loaded with berberine (BBR) and MnO2-coated black phosphorus nanosheets (BPNS@MnO2) for the microenvironment-adaptive treatment of infected burn wounds. The dynamic guar gum network endowed the hydrogel with injectability, self-healing ability, and conformal adaptability. BPNS@MnO2 exhibited pH-dependent enzyme-like activities, including OXD-like antibacterial activity under acidic conditions and SOD-/CAT-like ROS-scavenging activity under near-neutral conditions and endowed the hydrogel with NIR-triggered photothermal responsiveness. Moreover, NIR irradiation further enhanced the antibacterial efficacy and moderately enhanced BBR release from the hydrogel. In vitro, CBBM combined with NIR irradiation achieved potent antibacterial efficacy against S. aureus and E. coli under the tested conditions and reduced intracellular ROS levels. In vivo, the CBBM + NIR treatment accelerated infected burn wound healing, achieving a wound closure rate of 97.53 ± 2.01% by day 14, accompanied by reduced inflammation, enhanced collagen deposition, and increased expression of the angiogenesis-related markers VEGF and CD31. These results demonstrate that the CBBM hydrogel is a promising multifunctional guar gum-based dressing for infected burn wound healing by integrating local drug delivery, catalytic regulation, and photothermal activation.
Ziyi Zhao, Yanxiang Sang, Benyan Zheng et al.· International Journal of Bio...· 0 citations
To combat microbial infection and persistent inflammation of wounds, the increasing type and dosage of antibiotics in wound dressing results in the formation of drug-resistant bacteria, which seriously delays the healing of infected wounds. Thus, to develop alternative antibacterial wound dressings independent of antibiotics is imperative. In this work, we established a novel degradable hybrid nanohydrogel material (TAPP/Mn3O4@CS-GA) with antibacterial and anti-inflammation effects by loading 5,10,15,20-tetrakis (4-aminophenyl)-21H,23H-porphine (TAPP) with PDT function and Mn3O4 with SOD and CAT-like activities in chitosan hydrogel (CS-GA). The nanosystem can produce abundant ROS under laser irradiation, SOD and CAT-like activities of Mn3O4 generate enough O2 to provide substrate for PDT mediated by TAPP, increasing the concentration of singlet oxygen (1O2) and enhancing the PDT effect. After laser irradiation, SOD and CAT-like activities continue transfer superoxide anion free radical (O₂-·) and hydrogen peroxide (H2O2) to O2 to reduce inflammation caused by oxidative stress, relieve hypoxia and promote angiogenesis. The antibacterial experiments results show that the combination of antibacterial and anti-inflammation mediated by TAPP/Mn3O4@CS-GA hydrogel can accelerate infected wound healing.
Ningning Xu, Yu Liu, Shuling Yu et al.· International Journal of Bio...· 0 citations
Skin wound infection is a key factor that hinders the healing process and repair outcome of wounds, especially when it involves drug-resistant bacteria, which is extremely difficult to eliminate. Therefore, developing wound dressings with the ability to kill drug-resistant bacteria holds great value. Herein, carboxymethyl chitosan (CMCS) and 2,4,6-trihydroxybenzaldehyde (THBA)@silver ion chelates were assembled into a triple dynamically cross-linked hydrogel (CTA) through imine bonds, hydrogen bonds, and polyphenol metal chelate bonds. The CTA0.15 hydrogel exhibits sensitive near-infrared response properties. When exposed to 808 nm near-infrared light with a power density of 0.3 W/cm2, the temperature can easily rise to between 45 °C and 50 °C, enabling photothermal sterilization. Combined with the strong antibacterial activity of silver ions and the photothermal effect of the hydrogel, it can quickly (15 min) and completely eliminate common pathogenic bacteria (E. coli and S. aureus) and drug-resistant bacteria (MRSA) in vitro. In addition, this hydrogel also possesses injectability, tissue adhesiveness, self-healing property, shape adaptability, antioxidant capability, catalase (CAT)-like activity, and biocompatibility. The in vivo experiments and transcriptome analysis demonstrated that the combination of CTA hydrogel and NIR treatment significantly accelerated the healing process of MRSA-infected wounds by eliminating antibiotic-resistant bacterial infections, regulating inflammatory responses, promoting collagen deposition and angiogenesis.
Chenghao Li, Pengyuan Liu, Pei Cheng et al.· International Journal of Bio...· 0 citations
Drug-resistant bacteria infecting wounds and impeding their healing have become a pressing clinical challenge. Antimicrobial photodynamic therapy (aPDT) does not pose a risk of bacterial resistance, but its application is limited due to the short lifespan, restricted diffusion distance, and non-selective biological toxicity of reactive oxygen species (ROS). Herein, we developed a visible-light-responsive organic nanoplatform (iTPyPXs/SCM) that improves ROS utilization for antimicrobial therapy while limiting excessive intracellular ROS. The platform consists of cationized photodynamic organic nanoparticles (iTPyPXs) integrated with a silk fibroin-based nanofibrous membrane (SCM) via electrospray deposition. Cationization enhanced the local donor-acceptor (D-A) structure and electrostatic adhesion of iTPyPXs, improving visible-light-induced ROS generation at the bacteria-material interface. Meanwhile, SCM immobilized iTPyPXs and released silk fibroin to reduce excessive intracellular ROS, thereby supporting an M2-associated reparative immunomodulatory tendency. In a rat model, iTPyPXs/SCM-aPDT eradicated infection and accelerated wound closure, while promoting inflammation resolution, angiogenesis, and collagen deposition. Transcriptomic analysis further confirmed that the treatment promoted regenerative healing. Collectively, this work provides a safer and more effective biomaterial strategy for photodynamic therapy in infected wound healing.
Hongyu Lin, Qingyang Peng, Ying Lin et al.· Biomaterials· 0 citations