Nanotechnology-Based Modulation of Autoimmune Microenvironments in Sjögren's Syndrome: A Review of Mechanistic Perspectives.

Sjögren's syndrome (SS) refers to a chronic, systemic autoimmune disease that features infiltration of the exocrine glands by lymphocytes, dysfunction of the salivary and lacrimal glands, generation of autoantibodies, and deregulation of the immune system. Treatment of SS currently focuses on alleviating symptoms and immunosuppression without much success in repairing the damage and restoring immune tolerance. Growing research supports the view that the autoimmune microenvironment, comprising epithelial cells, immune cell populations, cytokines, oxidative mechanisms, and ectopic lymphoid tissue, is the key driver of disease initiation and development. Reprogramming the autoimmune microenvironment thus represents a new potential treatment approach. Immunomodulation is particularly well-suited to nanotechnology owing to its unique characteristics in drug targeting and delivery. In this review, the pathophysiological features of SS, as well as all the important therapeutic targets within the microenvironment of the autoimmune response, have been described in great depth. Moreover, recent progress made in nanotechnology platforms, including polymeric nanoparticles, lipid delivery systems, inorganic nanoparticles, biomimetic nanoparticles, and hydrogel nanotherapy, has been extensively discussed regarding their relevance towards achieving successful immune modulation and regenerating the salivary glands. Future directions regarding current research status, translational progress, precision nanomedicine, AI-based nanomaterials, and multi-functional smart nanomedicines have been included here.