Fe2+: Fe3+ Molar Ratio Influences the Immunomodulatory Properties of Maghemite (γ-Fe2O3) Nanoparticles in an Atopic Dermatitis Model

Here, we report the different antioxidant and physiological effects of maghemite nanopartides (gamma-Fe2O3 NPs) obtained using various Fe2+: Fe3+ molar ratios (FM1 = 1: 1, FM2 = 1: 2, and FM3 = 2: 3) via coprecipitation from ferrous/ferric salts. We investigated the physical, optical, and antioxidant properties of FM1, FM2, and FM3 nanopartides by conducting UV, Raman, FTIR, and EDX spectroscopic analyses along with DPPH radical scavenging activity. Results showed the highest DPPH scavenging activity in the FM2 group (50.76%), while the activity in the FM1 and FM3 groups was 23.60% and 34.63%, respectively. In addition, topical application of nanopartides induced significant but different anti-inflammatory and immunomodulatory effects in Dermatophagoides farinae extract/2,4-dinitrochlorobenzene (DFE/DNCB)-sensitized BALB/c mice. The FM2 treatment alleviates more effectively the DFE/DNCB-induced atopic dermatitis-like (AD-like) symptoms in mouse ears (edema, excoriation, scaling, and hemorrhage). In comparison with the DFE/DNCB-sensitized mice, FM2 treatment greatly reduced the size and weight of the spleen and the lymph nodes. It also suppressed mast cell infiltration (2-fold) and reduced dermal and epidermal thickness in mice. In addition, FM2 treatment exhibited better inhibition of the mRNA levels of Th1 (IFN-gamma and TNF-alpha) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, and IL-31), as well as the levels of various inflammation-related proteins (COX-2, iNOS, and TNF-alpha). Moreover, we demonstrated that an increasing proportion of Fe3+ in Fe2+: Fe3+ .- enhances the antioxidant activity and increases the anti-inflammatory and immunomodulatory effects of gamma-Fe2O3 NPs in an AD mouse model. Thus, gamma-Fe2O3 NPs could be used in the formulation of nonsteroidal drugs for AD treatment.