Unraveling the Interplay Between Nanosized Drug Delivery Systems and the Immune System: Mechanisms and Potential Implications

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Background

Nanomedicine is proving to be a valuable tool for novel therapeutic approaches. The incredible technological advancements achieved in recent years have made it possible to design nanosized drug delivery systems able to specifically respond to tissue-specific stimuli or to precisely target distinct cell populations. However, as for any type of non-self entity and therapeutic intervention, such engineered nano-systems will be confronted by our immune system. Owing to their size, akin to that of viruses, as well as their common entry routes into the body with pathogens, the sentinel function of the immune system can be triggered by nanomaterials, resulting in an array of readouts relevant to efficacy and immunotoxicity.

The study of the interactions occurring at the interface between nanosized drug delivery systems and the immune system is highly important to predict the biological fate of nano-based therapeutic interventions in terms of safety, efficacy, and toxicity. Indeed, enhanced understanding of the underlying molecular mechanisms that play a major role in the nano-immune system interplay will be crucial for the design of drug delivery systems with the potential to avoid innate immune system recognition and activation. On the other hand, the possibility to fully apprehend these mechanisms could enable the elucidation of systems that are capable of interacting with, and modulating, the immune system itself. For example, this could be the case of targeting the inflammatory microenvironment, which underlies many pathological conditions, but also may be relevant in the case of immuno-therapy or vaccine development.

The main aim of this Research Topic is to provide an updated overview of the mechanisms involved in the interaction between synthetic nanosized drug delivery systems and the immune system, and the potential strategies that allow us to take advantage of those interactions by ‘encrypting’ the molecular pathways they rely on. Moreover, we aim to discuss recent strategies based on biomimetic and exosome-like nanosystems and their immune-regulatory activity, and consequently explore the role of the protein corona as the entity that mediates those interactions. In addition, through this Topic, we want to open the discussion about the implications that the design and development of such nano-materials will have in terms of regulatory paths, manufacturing protocols and clinical translation. The answer to those concerns will provide an improved knowledge about the state of art in this field to the research community, including new tools and approaches for improving the well-being of patients.

Keywords: Nanomedicine, Immune System, Drug Delivery Systems, Innate Immunity, Immunotherapy

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