Two-dimensional GeTe nanosheets for psoriasis through modulation of macrophage activation and psoriatic inflammation

Abstract

Psoriasis is a chronic inflammatory disease characterized by thickened erythematous skin lesions covered with white and silvery scales and accompanied by macrophage infiltration into the dermis. Although 2-3% of the world's population suffers from psoriasis, there is still a requirement for novel, safe, and effective treatment options. Previously, our group demonstrated the theranostic effects of two-dimensional germanium telluride nanosheets (GeTe-NSs) in the treatment of inflammatory bowel disease. However, the precise mechanisms underlying their therapeutic action remained unclear. In this study, the specific anti-inflammatory mechanisms of GeTe-NSs in lipopolysaccharide-stimulated RAW 264.7 macrophages were evaluated, along with their therapeutic potential for psoriasis treatment in an imiquimod (IMQ)-induced murine model. GeTe-NS treatment significantly decreased cell proliferation and reduced the production of reactive nitrogen and oxygen species in activated RAW 264.7 macrophages. The GeTe-NSs lowered the mRNA levels of key pro-inflammatory mediators (Nos2, Tnf, Ccl2, and Cxcl15), while enhancing the mRNA levels of an anti-inflammatory factor (Arg1) and an antioxidant enzyme (Nqo1). Flow cytometric analysis revealed that the GeTe-NSs promoted a shift from the M1 (pro-inflammatory) macrophage phenotype toward the M2 (anti-inflammatory) phenotype. Western blot analysis demonstrated that anti-inflammatory effects were achieved by inhibiting the activation of the TLR4/CD14 and ERK/NF-kB/STAT1/STAT3 pathways. In vivo, the oral administration of GeTe-NSs in an IMQ-induced psoriasis mouse model resulted in significant improvements in clinical scores, epidermal thickening, and the proportions of M1/M2 macrophages in spleen and skin lesions. Taken together, these findings suggest that GeTe-NSs could be a promising nanomaterial for treating inflammatory diseases, including psoriasis.