Advances in Nrf2 Signaling Pathway by Targeted Nanostructured-Based Drug Delivery Systems

Nanotechnology has gained significant interest in various applications, including sensors and therapeutic agents for targeted disease sites. Several pathological consequences, including cancer, Alzheimer's disease, autoimmune diseases, and many others, are mostly driven by inflammation and Nrf2, and its negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (Keap1), plays a crucial role in maintaining redox status, the expression of antioxidant genes, and the inflammatory response. Interestingly, tuning the Nrf2/antioxidant response element (ARE) system can affect immune-metabolic mechanisms. Although many phytochemicals and synthetic drugs exhibited potential therapeutic activities, poor aqueous solubility, low bioavailability, poor tissue penetration, and, consequently, poor specific drug targeting, limit their practical use in clinical applications. Also, the therapeutic use of Nrf2 modulators is hampered in clinical applications by the absence of efficient formulation techniques. Therefore, we should explore the engineering of nanotechnology to modulate the inflammatory response via the Nrf2 signaling pathway. This review will initially examine the role of the Nrf2 signaling pathway in inflammation and oxidative stress-related pathologies. Subsequently, we will also review how custom-designed nanoscale materials encapsulating the Nrf2 activators can interact with biological systems and how this interaction can impact the Nrf2 signaling pathway and its potential outcomes, emphasizing inflammation.