## 4 Nanostructured Systems for Immunotherapeutic Delivery in Non- Malignant Applications
### Allergic and Inflammatory Disorders  
Inflammation represents a multifaceted physicochemical response of living tissues subjected to physical or chemical aggression, comprising the activation of enzymes, mite gyration of cells, the breakdown of tissues, and the release of mediators [139]. Inflammation is a common factor in numerous conditions, including obesity, diabetes, allergies, psychiatric diseases, and skin disorders [140; 141; 142], being an important process to target to alleviate associated symptoms. Inflammatory diseases are generally managed by administering anti-inflammatory drugs. Nonetheless, conventional anti-inflammatory agents lack tissue specificity, may produce systemic side effects, and exhibit limited efficacy in crossing biological barriers. To overcome these challenges, nanomaterials can be used to deliver anti-inflammatory agents to enhance their activity, especially as nanoparticles can interact with the components of the immune system in several ways. In more detail, the influence of nanoparticles on T/B lymphocytes, neutrophils, monocytes/macrophages, dendritic cells, natural killer (NK) cells, and inflammation-related molecules is displayed in Figure 8[27]. For instance, [PERSON] and colleagues [114] fabricated a nanoformulation based on hyaluronic acid and bilirubin to manage the inflammation of the colonic epithelium. The nanomedicine was tested on a murine model of acute colitis, leading to encouraging results. Namely, the proposed strategy restored the epithelium barriers, modulated gut microbiota, regulated innate immune responses, and displayed promising therapeutic efficacy against targeted conditions, thus representing a good candidate for treating inflammatory diseases. On a different note, a few studies reported the implication of nanomaterials in allergen-specific immunotherapy as they offer advantages as both carriers and adjuvants [143; 144]. For example, [PERSON] et al. [18] have evaluated the immunological effects of intravenously administered graphene nanosheets and MWCNTs, focusing on their capacity to induce site-specific Th2 inflammatory responses through the IL-33/ST2 signaling axis. The researchers showed that both nanomaterials trigger a Th2-skewed immune response characterized by elevated levels of IL-33 and its receptor ST2, producing localized inflammation. The shift inTh1/Th2 balance may further impact host defense and exacerbate allergic diseases like asthma and anaphylaxis; these immunotoxicological effects may be attributed to the varied physicochemical properties of the delivery vehicles. Overall, the study emphasized the  
Figure 8: Schematic illustration of the interactions between nanoparticles and immune system components in managing inflammatory diseases. Reprinted from an open-access source [27]. potential immunomodulatory effects of graphene-based and carbon nanotube nanomaterials, highlighting the importance of understanding their biological interactions to safe biomedical applications. On the other hand, [PERSON] et al. [145] focused their research on fullerenes, investigating their immunotherapeutic role. The researchers have evaluated the impact of these CBNs on allergic responses, demonstrating that these nanomaterials effectively inhibit allergic reactions by modulating immune responses. The study results reveal that fullerenes can reduce the production of key pro-inflammatory cytokines and suppress immune cells' activation in allergic pathways. These findings suggest that fullerene nanomaterials hold potential as therapeutic agents for managing allergic diseases, offering a novel approach to modulate immune function and mitigate allergic responses in mast cell-dependent conditions like asthma, inflammatory arthritis, heart disease, and multiple sclerosis. Alternatively, the study conducted by [PERSON] and colleagues [146] has explored the use of biodegradable protamine nanoparticles loaded with CpG-oligodeoxynucleotides (CpG-ODN) in preventing allergen-induced Th2 immune responses in BALB/c mice.