## 4 Nanostructured Systems for Immunotherapeutic Delivery in Non- Malignant Applications
### Autoimmune Diseases  
Autoimmune disorders are chronic ailments in which the immune system misidentifies and destroys the body's own cells, tissues, or organs due to a breakdown in self-tolerance and regulatory mechanisms. This imbalance, which includes complicated antigenic responses from both the adaptive and innate immune systems, can result in chronic inflammation and tissue damage. Diseases such as systemic lupus erythematosus (SLE) are usually \begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**ClinicalTrials.gov ID** & **Official Title** & **Study Type** & **Intervention** & **Enrollment (Estimated)** &
\begin{tabular}{c} **Study** \\ **Completion** \\ **(Estimated)** \\ \end{tabular} & **Ref.** \\ \hline \multirow{6}{*}{NCT04159337} & A Prospective Study on Companion Diagnosis by NGS-based Large-panel in Targeted Drug Delivery and Immunotherapy of Lung Cancer & \multirow{2}{*}{Observational detection} & Other: The method of gene mutation detection & \multirow{2}{*}{2000} & \multirow{2}{*}{31 May 2022} & \multirow{2}{*}{[106]} \\ \cline{1-1} \cline{5-5}  & A Phase 1b Study of Chemo-immunotherapy With Pegylated liposomal Doxorubicin (Doxorubicin (Doxil/Caelyx) and Pembrolizumab (Keytruda) in Metastatic Endocrine-resistant Breast Cancer & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Summary of clinical trials concerning drug delivery systems for cancer immunotherapy available on ClinicalTrials.gov as of August 2024.  
treated with broad immunosuppressive treatments, which can slow disease development but rarely provide a cure, and frequently cause major side effects [5; 21; 108; 109]. Recent advances in nanobiotechnology have resulted in the creation of tailored nanoparticles that target homeostatic regulatory deficiencies and promote the regeneration of therapeutic antigen-specific Tregs. These nanoparticles can target antigen-presenting cells or directly impact T cells, inducing and expanding protective Tregs of both CD4\({}^{+}\) and CD8\({}^{+}\) kinds. Some nanoparticles even resemble tolerogenic antigen-presenting cells. Because of their versatility, nanoparticles are being studied for autoimmune disease management, as transporters for biological agents and drugs, as anti-inflammatory substances, and as tools for developing immunological tolerance [21; 109]. Several interesting studies have explored the utilization of nanostructured systems in experimental autoimmune encephalomyelitis (EAE) models. One of the first studies on this topic was conducted by [PERSON] et al. [110], who investigated how carbon nanotubes internalized by antigen-presenting cells (APCs) influence the development of encephalitogenic CD4\({}^{+}\) T-cell lines, potentially altering autoimmune disease progression. Nonetheless, the authors considered that further research was needed to fully assess carbon nanoparticles' therapeutic potential and safety due to their hydrophobic nature and unclear clearance mechanisms. A few years later, [PERSON] et al. [111] tackled a different material for creating nanotube-based carriers. Specifically, the researchers explored the role of Ti-O-based nanomaterials such as H2 Ti3O7 nanotubes (TNT) and anatase TiO2 fine particles (TFP) in models of EAE and collagen-induced arthritis (CIA), revealing the potential use of these nanomaterials in alleviating pathophysiology signs and reducing pro-inflammatory cytokine HMGB1. Based on the obtained results, the authors concluded that Ti-O-based nanomaterials can be applied in the treatment of multiple sclerosis or rheumatoid arthritis. Differently, [PERSON] and colleagues [112] explored the therapeutic potential of intraperitoneally administered signred graphene quantum dots (GQD). The nanomaterials reduced immune infiltration, demyelination, axonal damage, and cell death in the central nervous system (CNS) of EAE animals. GQD treatment also lowered the numbers of Th1 cells, the expression of the Th1 transcription factor T-bet, and proinflammatory cytokines.