Visible-light-responsive cationized photodynamic nanoparticles integrated with a silk fibroin-based nanofibrous matrix for enhanced ROS utilization in infected wound healing.
A visible-light-responsive organic nanoplatform (iTPyPXs/SCM) that improves ROS utilization for antimicrobial therapy while limiting excessive intracellular ROS and provides a safer and more effective biomaterial strategy for photodynamic therapy in infected wound healing is developed.
Abstract
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.
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.
Weiwei Zhang, Lixiang Fan, Xuanjun Zhang et al.· ACS Applied Materials and In...· 0 citations
Bacterial infections, particularly those involving biofilm formation and antibiotic-resistant pathogens, severely impede wound healing. Photodynamic antibacterial therapy (PDT) offers a non-antibiotic, broad-spectrum antibacterial strategy via light-triggered reactive oxygen species (ROS) generation, yet poor photosensitizer retention and instability in exudative wounds limit its clinical translation. Herein, we report a crosslinker-free photodynamic hydrogel platform based on a physically assembled poly(vinyl alcohol) (PVA) network incorporating a water-soluble cyclometalated Ir(III) photosensitizer in its sodium salt form (IrONa). The hydrogel is fabricated via repeated freeze-thaw cycling, enabling homogeneous photosensitizer incorporation without chemical crosslinkers. Multivalent hydrogen bonding and nanoscale physical confinement effectively suppress premature photosensitizer leaching while preserving its photophysical activity. Upon visible-light irradiation, the FT-PVA/IrONa hydrogel generates sustained singlet oxygen with high efficiency, resulting in potent antibacterial activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Notably, localized photodynamic action reduced mature biofilm biomass and viable biofilm-associated bacteria, resulting in a 71.2% inhibition rate against MRSA biofilms. In an MRSA-infected burn wound model, photodynamic activation of the FT-PVA/IrONa hydrogel significantly decreases bacterial burden, downregulates pro-inflammatory cytokines, and upregulates pro-angiogenic markers, ultimately accelerating wound closure and tissue reconstruction. This work establishes a simple yet effective strategy to embed photosensitizers into tissue-conformal hydrogels, offering an antibiotic-free platform for infected wound treatment.
Tian Luan, Yu Zhang, Weijin Zhu et al.· Journal of materials chemist...· 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.
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
Currently, monkeypox virus (MPXV) treatment methods face a dilemma of potential drug resistance. They cannot simultaneously address two core pathological mechanisms driving infection: continuous viral replication and uncontrolled inflammatory storm. To overcome these challenges, we innovatively developed a dual-function therapeutic strategy with precise virus clearance and anti-inflammatory effects, constructing a dual hydrogel system synergistically combining phototherapy and immunomodulatory effects. Specifically, aggregation-induced emission (AIE) nanoparticles (NPs) are embedded in a reactive oxygen species (ROS)-degradable polyvinyl alcohol (PVA)-N1-(4-borobenzoyl)-N3-(4-borobenzoyl)-the N1, the N1, N3, N3-tetramethylpropane-1,3-diamine (tsPBA) hydrogel, while the anti-inflammatory agent is loaded in a zwitterionic hydrogel (SBMA) matrix. Under near-infrared band laser irradiation, AIE NPs efficiently generate large amounts of ROS, which, together with inflammation-produced endogenous ROS, trigger the rapid degradation of the ROS-responsive hydrogel and release of AIE NPs. The generated ROS effectively destroys the MPXV shell and strongly inactivates the virus. After virus clearance, the SBMA hydrogel continuously releases anti-inflammatory drugs (Dexamethasone, DXMS) to inhibit excessive pro-inflammatory cytokines and reduce inflammation-induced tissue damage. In mouse, rabbit, and non-human primate models with MPXV-induced skin damage, this hydrogel nanoparticle protective layer significantly inhibits viral replication and accelerates wound healing, representing a transformative, convertible platform for treating MPXV and other highly inflammatory viral infections.
Ning Shi, Xinyu Cao, Xiaolong Zhu et al.· Biomaterials· 0 citations
Skin wounds are highly susceptible to bacterial invasion, and persistent infection remains a major obstacle to effective tissue repair. Conventional wound dressings often show insufficient antibacterial activity and limited capacity to actively regulate the infected wound microenvironment. Herein, an acid-responsive nanozyme-loaded composite fibrous membrane was developed as a non-antibiotic wound dressing for enhanced chemodynamic antibacterial therapy. Silver nanocubes were encapsulated within zeolitic imidazolate framework-67 to form Ag@ZIF-67 nanozymes, which were subsequently incorporated into electrospun polycaprolactone fibers to obtain Ag@ZIF-67/PCL composite membranes. Under weakly acidic conditions mimicking infected wounds, the ZIF-67 shell underwent microenvironment-triggered decomposition, enabling sustained release of Co2⁺ and Ag⁺. The released Co2⁺ catalyzed the conversion of H₂O₂ into highly toxic hydroxyl radicals through a Fenton-like reaction, while Ag⁺ provided additional broad-spectrum antibacterial activity. Benefiting from this complementary antibacterial mechanism and the extracellular matrix-like fibrous architecture, the Ag@ZIF-67/PCL membrane achieved antibacterial efficiencies exceeding 98% against both Escherichia coli and Staphylococcus aureus after 48 h. Moreover, the composite membrane exhibited favorable cytocompatibility and hemocompatibility, promoted endothelial cell migration, and significantly accelerated the healing of S. aureus-infected wounds in vivo by enhancing re-epithelialization, collagen deposition, and neovascularization. Overall, this study provides a pH-responsive, nanozyme-integrated fibrous membrane with combined antibacterial and pro-regenerative functions, offering a promising strategy for the treatment of bacteria-infected wounds without relying on antibiotics.
Han Lin, Jingyan Huang, Xiaoqi Xie et al.· Colloids and Surfaces B: Bio...· 0 citations