Poly(Methylqinjgtebie Methacrylate) Nanoparticles-Based HIF-1α Carrier Reduces Epithelial Cell Activation and Adhesion Molecule Expression in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a skin disease. This study established a mouse AD model to investigate the impact of PMMA (Poly(methyl methacrylate)) nanoparticles (PMMANPs) on epithelial cells. Nice (n = 30) receiving no intervention were taken as a healthy group, while the other animals (n = 30) were placed in the model group and sensitized with 2,4-Dinitrochlorobenzene (DNCB) acetone solution to establish the AD model. Skin epithelial cells on the backs of mice were assigned into blank control group, negative control group, PMMA group, Hypoxia-Inducible Factor (HIF)-1α group, and PMMA + HIF-1α group, followed by analysis of epithelial cell density by toluidine blue staining, HIF-1α, ICAM-1 (Intercellular Adhesion Molecule 1) and VCAM-1 (Vascular cell adhesion molecule-1) expressions. The back skin of mice in the model group appeared with edema, erythema, and desquamation, with increased number of scratches and pathological changes such as skin keratinization, inflammatory cell infiltration, and epidermal thickening, indicating successful establishment of the AD model. In comparison, the epithelial cell density of the PMMA group, HIF-1α group, and PMMA+HIF-1α group (10.08±0.32, 10.50±0.34, 7.52±0.28) decreased significantly (P <0.05), with lowest density in the PMMA+HIF-1α group. Importantly, treatment with HIF-1α, PMMANPs, and HIF-1α-loaded PMMANPs greatly elevated HIF-1α levels (3.25±0.08, 3.69±0.07, 4.46±0.10) while decreased ICAM-1 and VCAM-1 levels (794.02±56.27, 788.36±49.38, 744.64±36.40). Furthermore, combined treatment obtained highest HIF-1α expression and lowest ICAM-1 and VCAM-1 level (P <0.05) expressions. Collectively, the PMMANPs carrying HIF-1α VCAM-1 exerted protective role in the recovery of AD, and these findings suggest that, the HIF-1α can be used as a target gene for AD treatment.