Melittin-Loaded Fe3O4-Aushell Nanocomposite Hydrogel for Multifunctional Treatment of Atopic Dermatitis

Background: Atopic dermatitis (AD) severely impairs the lives of patients and existing therapies are limited by side effects or insufficient efficacy. In this study, we developed a multifunctional nanocomposite hydrogel that integrates immunoregulation, antioxidant, antibacterial, and skin repair for the integrative treatment of AD. Methods: Fe 3 O 4 -Au shell (FA) nanoparticles (NPs) were synthesized, melittin (MLT) was anchored onto FA NPs, and MLT-Fe 3 O 4 -Au shell (MFA) was loaded into Pluronic F-127 (PF127), to prepare the MFA@PF127 hydrogel. After a comprehensive evaluation of the physicochemical properties, MFA@PF127 was incubated with HaCaT cells and administered to AD lesions to demonstrate its therapeutic efficiency for AD in vitro and in vivo. Results: The Fe 3 O 4 ‑Au shell (FA) NPs with a heterodimer morphology and uniform size were successfully prepared, and the MLT was then loaded onto FA NPs with a high loading efficiency of 64.5%. By loading MLT-FA (MFA) NPs into PF127, the MFA@PF127 nanocomposite hydrogel with thermosensitivity, a porous structure, and good biocompatibility was successfully constructed. After incubation with MFA@PF127 and irradiated with near-infrared (NIR) laser, HaCaT cells showed significantly lower thymic stromal lymphopoietin (TSLP) expression and reactive oxygen species (ROS) levels than the control. The growth of S. aureus and biofilm formation were suppressed by MFA@PF127 under NIR irradiation. When administered to AD lesions, MFA@PF127+NIR significantly alleviated the dermatitis severity score; downregulated TSLP, IL‑4, and IL‑13 expression, suppressed S. aureus colonization; reduced ROS levels; and alleviated epidermal thickening and mast cell infiltration. Conclusion: MFA@PF127 exhibited multifunctionality of immunoregulation, and antioxidant and antibacterial activities, which significantly alleviated AD symptoms in a mouse model and provided a potential strategy for AD treatment after further preclinical validation.