Nanoparticle-Mediated Signaling Rewiring and Reprogramming of Immune Responses

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Background

Recent advances in the understanding of the different effector signaling pathways on immune cells are at the core of better immunomodulatory approaches. For example, these manipulations allow us to re-train T-cells to prevent autoimmune attacks and to rewire them to switch towards an active protective immunophenotype. Besides, it has been lately observed how immune cells can adapt energy metabolism requirements and that metabolic sensing is coupled to signal transduction pathways that determine cell fate. These phenomena are being related now to the onset and/or severity of several diseases based on inadequate immune responses like multiple sclerosis, rheumatoid arthritis, diabetes or Alzheimer’s disease, and also exploited to develop cancer immunotherapy. Unifying our understanding of the metabolism and the effector signaling pathways might represent an efficient strategy to identify drugs or endogenous molecules in order to rewire and reprogram immune cells for therapeutic purposes in many diseases associated with dysregulation of the immune system.

However, in the absence of temporal control and cellular and intracellular specificity, the application of these reprogramming tools will presumably cause off-target effects and the absence of precise reversibility. Besides, drug limitations include short half-life (high-doses as an alternative) and/or low bioavailability into the body.

Nanoparticle-based delivery systems are gaining momentum because they allow the development of a precision-based medicine for reprogramming and dynamic rewiring of signaling pathways in immune cells. Even without any particular targeting strategy, several studies have shown the feasibility of reprogramming circulating inflammatory immune cells after intravenous administration of different nanoparticles exploiting just their physical properties. In this sense, it is possible to differentially reprogram these cells to favor their homing to injured locations promoting neuroprotection or to reduce the traffic to inflamed areas limiting immune-associated pathology. Immune-reprogramming nanoparticles have been shown to redirect suppressive macrophages to act as anti-tumor effector cells, and without the described side-effects observed, for example, with checkpoint inhibitors. In this sense, several clinical trials are underway to bring immune-reprogramming nanoparticles to patients and there is a critical mass of proof of concept studies on nanoparticles tailored with different biological and chemical strategies to modify the response of immune cells. Also, nanoparticle reprogramming of macrophages and T-cells mediated responses is having a major impact on the development of new methods for cancer immunotherapy. One aspect of special relevance is the genetic reprogramming of immune cells based on nanoparticles from the generation of chimeric antigen receptor (CAR) transgene cassettes in T cells to RNAi rewiring strategies in macrophages.

This Research Topic will address the most recent updates in the field of nanoparticles for immune cell reprogramming and rewiring. We are interested in studies that cover basic aspects of the immune function to those addressing pathologies associated with an immune imbalance including cancer immunotherapy.

We welcome authors to submit Original Research, Reviews, Mini Reviews, Perspectives, and Clinical Trials articles focusing on, but not limited to, the following topics:

1. Nanoparticle-mediated regulation of metabolic control in immune cells. In vitro and in vivo.
2. Impact of nanoparticle-mediated genetic-engineering of immune cells on immune reactions.
3. Nanoparticle approaches for reprogramming immune cells in aging and neurodegeneration.
4. Nanoparticle-mediated enhancing of cancer immunotherapy strategies based on
reprogramming/rewiring of immune cells.
5. Smart rewiring of inflammation and autoimmunity processes.
6. Synthesis of new nano-based platforms targeting immune cells.
7. Nano-inspired systems biology and reprogramming/rewiring immune responses.


Dr. Quintana is the founder of AnTolRx. The other Topic Editor declares no competing interests.

Keywords: Cell signaling, Autoimmunity, Inflammation, Reprogramming, Rewiring, Nanoparticles, Immunotherapy, Immunoregulation

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