Immunomodulatory nanosystems for treating inflammatory diseases

Inflammatory disease (ID) is an umbrella term encompassing all illnesses involving chronic inflammation as the central manifestation of pathogenesis. These include, inflammatory bowel diseases, hepatitis, pulmonary disorders, atherosclerosis, myocardial infarction, pancreatitis, arthritis, periodontitis, psoriasis. The IDs create a severe burden on healthcare and significantly impact the global socio-economic balance. Unfortunately, the standard therapies that rely on a combination of anti-inflammatory and immunosuppressive agents are palliative and provide only short-term relief. In contrast, the emerging concept of immunomodulatory nanosystems (IMNs) has the potential to address the underlying causes and prevent reoccurrence, thereby, creating new opportunities for treating IDs. The IMNs offer exquisite ability to precisely modulate the immune system for a therapeutic advantage. The nano-sized dimension of IMNs allows them to efficiently infiltrate lymphatic drainage, interact with immune cells, and subsequently to undergo rapid endocytosis by hyperactive immune cells (HICs) at inflamed sites. Thus, IMNs serve to restore dysfunctional or HICs and alleviate the inflammation. We identified that different IMNs exert their immunomodulatory action via either of the seven mechanisms to modulate; cytokine production, cytokine neutralization, cellular infiltration, macrophage polarization, HICs growth inhibition, stimulating T-reg mediated tolerance and modulating oxidative-stress. In this article, we discussed representative examples of IMNs by highlighting their rationalization, design principle, and mechanism of action in context of treating various IDs. Lastly, we highlighted technical challenges in the application of IMNs and explored the future direction of research, which could potentially help to overcome those challenges.