Anti-bacterial layer coated Zn-doped mesoporous silica drug-carry platform for infected wound healing by inhibiting ferroptosis via the AMPK/Nrf2 axis.
Jul 2026· Biochemical and Biophysical Research Communications - BBRC· Vol 830, pp.
154271
· 0 citations· 28 references
Medicine
TL;DR
It is demonstrated that Ba@Zn-MSN@CH accelerated infected wound healing by inhibiting ferroptosis through activation of the AMPK/Nrf2 signaling pathway, highlighting the potential of baicalein-based nanotherapeutics as a promising strategy for infected wound management.
Abstract
Impaired infected wound healing is closely associated with mitochondrial dysfunction, and ferroptosis has emerged as a key mechanism connecting oxidative stress to mitochondrial damage. Baicalein holds potential for modulating this process, yet its application is constrained by poor bioavailability. Herein, a multifunctional nano-delivery system (Ba@Zn-MSN@CH) was rationally designed for infected wound treatment. Zinc-doped mesoporous silica nanoparticles (Zn-MSN) were synthesized to serve as a baicalein carrier. Carboxymethyl chitosan (CMCS) and dihydrocaffeic acid were covalently grafted onto the surface of the nanoparticles via silanization and amidation reactions, leading to the formation of a stable core-shell structure. The introduction of macromolecular coating was found to not only prolong drug release but also enhance antioxidant and antibacterial efficacy. What's more, Ba@Zn-MSN@CH effectively alleviated mitochondrial damage by inhibiting ferroptosis, thereby restoring cell proliferation, migration, and angiogenesis, and ultimately accelerating infected wound healing. Mechanistically, Ba@Zn-MSN@CH inhibited ferroptosis by inducing AMP-activated Protein Kinase α (AMPKα) phosphorylation in fibroblasts. AMPKα sustained the abundance of nuclear factor erythroid 2-related factor 2 (Nrf2), which subsequently suppressed lipid peroxidation and inhibited ferroptotic cell death through upregulation of downstream antioxidant factors. Collectively, these findings demonstrated that Ba@Zn-MSN@CH accelerated infected wound healing by inhibiting ferroptosis through activation of the AMPK/Nrf2 signaling pathway, highlighting the potential of baicalein-based nanotherapeutics as a promising strategy for infected wound management.
A core–shell-type ZnO@ZIF-8/Ag nanocomposite material that combines high antibacterial activity with excellent biocompatibility offers a strategy for developing therapies against drug-resistant bacterial infections with the potential for clinical application.
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.
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
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
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.
Hongyu Lin, Qingyang Peng, Ying Lin et al.· Biomaterials· 0 citations
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