Ferroptosis‐Mediated Synergistic Therapy of Hypertrophic Scarring Based on Metal–Organic Framework Microneedle Patch

Abstract

Hypertrophic scarring, an abnormal fibroproliferative wound-healing disease, has brought tremendous burden for global healthcare systems. To date, no satisfactory treatment of hypertrophic scarring is available yet. Ferroptosis, an iron-dependent form of cell death, has attracted much attention recently for the therapy of diseases featuring iron addiction. Intriguingly, myofibroblasts derived from hypertrophic scarring are found to exhibit a high iron state which appears to be sensitive to trigger ferroptosis for scarring treatment. Accordingly, in this study, a pH responsive self-assembly nanoplatform is designed by encapsulating silver nanoclusters (AgNCs) and Chinese herbal medicine trigonelline (TRG) into zeolitic imidazolate framework-8 (ZIF-8) for synergistic ferroptosis therapy against hypertrophic scarring. The fabricated AgNC/TRG/ZIF-8 composites exhibit good biocompatibility and pH responsive-degradation inside myofibroblasts. The ZIF-8 precursors can increase the generation of lipid reactive oxygen species and deplete intracellular glutathione (GSH). Also, AgNCs have the capability to consume GSH, while TRG can inhibit the activity of glutathione peroxidase. Consequently, the synergistic ferroptosis anti-scarring therapy can be effectively achieved. Furthermore, AgNC/TRG/ZIF-8-loaded microneedle patches made of gelatin methacrylate show remarkable therapeutic effect against hypertrophic scarring on a rabbit ear model. This study suggests the great potential of ferroptosis-mediated strategy for treating fibrotic skin diseases in future clinical application.

Zeolitic imidazolate framework-90 loaded with methylprednisolone sodium succinate effectively reduces hypertrophic scar in vivo

“…The MPSS@ZIF-90 exhibited a promising therapeutic effect in HS treatment within a short period, while several months are required in the recently reported drug delivery systems and current clinical therapies. 4,50–52 Our investigations on experimental wound models in rabbit ears exhibited the effective treatment of MPSS@ZIF-90 in accelerating wound healing processes, and inhibiting the expression of HS-related proteins.…”

Microneedle Patch Integrated with Porous Silicon Confined Dual Nanozymes for Synergistic and Hyperthermia‐Enhanced Nanocatalytic Ferroptosis Treatment of Melanoma

“…Recently, MNs loaded with nanocomplex have been reported for ferroptosis-mediated synergistic wound therapy. [53] In addition, the antibacterial infection effect of MNs encapsulated with photothermal nanozyme have also been proven. [54] Encouraged by the previous works and remarkable nanocatalytic performance of the CuGQD/PdNPs@PSi in vitro, we further integrated CuGQD/PdNPs@PSi into the ultralive hyaluronic acid (HA) matrix to develop a dissolvable microneedle patch specifically for melanoma treatment.…”

Application and progress of new technologies and new materials in the treatment of pathological scar

“…The depletion of GSH is the main cause of ferroptosis ( Li et al, 2023 ). Studies have shown that myofibroblasts in HTS exhibit high iron levels, which can be targeted for “Ferroptosis-mediated scarring therapy.” To this end, Zhao et al (2023) developed a new ferroptosis-based nanoplatform by combining AgNC/TRG/ZIF-8 with the GelMA MN patch. In acidic environment, ZIF-8 is easy to degrade and release Zn2+ and 2-methylimidazole ligand.…”