## 4 Nanostructured Systems for Immunotherapeutic Delivery in Non- Malignant Applications
### Autoimmune Diseases
The protective effects were linked to the activation of MAPK/Akt signaling. GQD further protected neurons and oligodendrocytes from T cell-mediated damage, highlighting its potential to alleviate immune-mediated CNS damage during neuroinflammation. Nanotechnological approaches may also come in handy for improving the management of inflammatory bowel diseases (IBD). IBD pathogenesis is not fully understood, but it is known to involve a complex interplay between the mucosal immune system and the commensal gut microbiome. This condition, including ulcerative colitis (UC) and Crohn's disease (CD), is related to disrupted intestinal barrier function, microbial imbalance, and dysregulated immune responses to gut bacteria. Conventional IBD treatments are centered on managing the symptoms by suppressing immune responses. However, they often fail to address underlying issues like damage to the mucus layer and dysbiosis, which are also associated with significant systemic side effects and long-term complications, including infections, autoimmunity, and liver toxicity IBD [113; 114]. To overcome these drawbacks, [PERSON] et al. [115] proposed the utilization of GQD. After GQD intraperitoneal injection, macrophages were switched from classically activated M1 to M2, Tregs intestinal infiltration was enhanced, and excessive inflammation was alleviated through the regulation of immune cells. The results suggest the potential use of GQD in treating autoimmune disorders, including IBDs. Among autoimmune diseases, systemic lupus erythematosus (SLE) is marked by an imbalance between effector and regulatory T cells. Limited efficacy has been reported for current treatments, which are also responsible for serious side effects. Aiming to overcome these drawbacks, [PERSON] et al. [116] addressed the potential use of microRNA-125a (miR-125a), an agent known to play an important role in stabilizing regulatory T cells, but it is significantly downregulated in SLE patients. Specifically, the researchers developed a nanoparticle delivery system (monomethoxy (polyethylene glycol)-poly(d,l-lactide-coglycolide)-poly(l-lysine) (mPEG-PLGA-PLL)) to protect the cargo from degradation and deliver miR-125a into splenic T cells. This approach effectively reversed T cell imbalance and attenuated disease progression, offering a promising therapeutic strategy for SLE. One more interesting study concerning auto-immune diseases was identified to present an alternative solution for treating vitiligo. [PERSON] and colleagues [117] synthesized nanoparticles containing rapamycin and the autoanti HEL46-61 (NPHEL46-61/Rapa) to evaluate their effects on vitiligo. When TrpHEL mice bone-marrow-derived dendritic cells (BMDCs) were treated with NPHEL46-61/Rapa, expressions of the costimulatory molecules CD80 and CD86 were reduced. In vitro, these treated BMDCs inhibited antigen-specific CD4\({}^{+}\) T cell proliferation while promoting Treg development. Administering NPHEL46-61/Rapa to TCR-TrpHEL mice reduced vitiligo, boosted Treg production, and changed cytokine production by decreasing IFN-\(\gamma\) and IL-6 and raising IL-10. According to the study, these nanoparticles can establish antigen-specific immune tolerance, potentially preventing vitiligo.