This study investigates the therapeutic efficacy of zinc sulfide nanoparticles (ZnS NPs) encapsulated within adipose-derived mesenchymal stem cell exosomes (EXO-ZnS NPs) in an imiquimod-induced rat model of psoriasis, aiming to combine nanotechnology and regenerative medicine for enhanced immune modulation and skin repair. Adipose mesenchymal stem cells (AD-MSCs) were cultured and characterized, exosomes were isolated and validated by flow cytometry and TEM. ZnS NPs were synthesized, confirmed by XRD and TEM, and encapsulated into exosomes. Release profiles, Clinical (PASI scoring), histopathological, inflammatory and proliferative markers as well as immunohistochemical analyses were evaluated across control, psoriasis, and treatment groups (EXO, ZnS NPs, and EXO-ZnS NPs). EXO-ZnS NPs exhibited a uniform nanosize with sustained ZnS NPs release (80.5% over 24 h). In vivo, EXO-ZnS NPs significantly attenuated psoriatic symptoms, and Severity Index scores, reduced inflammatory mediators (IL-23, IL-17a, TNF-α, MCP-1, NLRP3), mitigated oxidative stress, downregulated proliferative markers (Ki-67, MMP-9), and inhibited VEGF-mediated angiogenesis. collectively restored epidermal structure and improved skin architecture. EXO-ZnS NPs synergistically combine the regenerative and immunomodulatory effects of exosomes with the intrinsic anti-inflammatory and antioxidant activities of ZnS NPs, offering a novel promising, dual-action therapeutic platform for effective and sustained psoriasis management.
