Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing.

Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

Wound Healing*/drug effects ; Reactive Oxygen Species*/metabolism ; Metal-Organic Frameworks*/chemistry ; Metal-Organic Frameworks*/pharmacology ; Inflammation*; Animals ; Mice ; Superoxide Dismutase/metabolism ; Porosity ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; RAW 264.7 Cells ; Male ; Ferroptosis/drug effects ; Macrophages/drug effects ; Macrophages/metabolism ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Diabetes Mellitus, Experimental ; Nanoparticles/chemistry ; Humans ; Antioxidants/pharmacology ; Nanocomposites/chemistry ; Membrane Proteins

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal-organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.
(© 2024. The Author(s).)

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81971839 National Natural Science Foundation of China; 81971840 National Natural Science Foundation of China

Keywords: Diabetic wound; Ferroptosis; Nanozymes; STING; Senescence

0 (Reactive Oxygen Species)
0 (Metal-Organic Frameworks)
EC 1.15.1.1 (Superoxide Dismutase)
0 (Antioxidants)
0 (Sting1 protein, mouse)
0 (Membrane Proteins)

Date Created: 20240512 Date Completed: 20240512 Latest Revision: 20240709

20240710

PMC11089722

10.1186/s12951-024-02423-6

38735970