Regulating trained immunity with nanomedicine

Trained immunity refers to a hyperresponsive functional state of the innate immune system, which is induced by certain stimuli, such as infections or vaccination. Trained immunity plays a key part in a variety of diseases, including cancer and inflammation, and is regulated through epigenetic and metabolic reprogramming of haematopoietic stem and progenitor cells in the bone marrow, giving rise to hyperactive myeloid cells. Nanomaterials inherently interact with phagocytic myeloid cells and are thus ideal platforms with which to regulate trained immunity. In this Review, we discuss the key pathways of trained immunity and investigate nanomedicine strategies to therapeutically regulate trained immunity. Nanomedicine can be applied not only to induce trained immunity to treat cancer or to enhance resistance to infections, but also to manage hyperinflammation and maladaptive trained immunity in a variety of clinical scenarios. We conclude with an outlook to future possibilities and some remaining challenges for nanomedicine approaches in trained immunity regulation

Nanoengineering Apolipoprotein A1-Based Immunotherapeutics

In the slipstream of targeting the adaptive immune system, innate immunotherapy strategies are being developed. In this context, technologies based on natural carrier vehicles that inherently interact with the innate immune system, are increasingly being considered. Immunoregulatory nanotherapeutics based on natural apolipoprotein A1 (apoA1) are discussed here. This protein is a helical, amphipathic macromolecule and the main constituent of high-density lipoprotein. In that capacity, apoA1 interacts specifically with innate immune cells, such as monocytes and macrophages, to collect and transport lipophilicmolecules throughout the body. Exactly these unique features make apoA1 a compelling elementary constituent of biocompatible self-assembled nanotherapeutics. Such apoA1-based nanotherapeutics (A1-nanotherapeutics) can be engineered and functionalized to induce or mitigate an innate immune response or to orchestrate an adaptive immune response through antigen delivery to dendritic cells. The authors first discuss apoA1's properties and how these can be exploited to generate libraries of A1-nanotherapeutics using advanced manufacturing approaches such as microfluidics or continuous flow methods. Using high-throughput in vitro screening methods and in vivo imagingto identify promising formulations are then recommend. Finally, Three distinct immunotherapy strategies are proposed to effectively treat a variety of diseases—including cancer, infection, and cardiovascular disease—and promote allograft survival in transplantation

Nanoengineering Apolipoprotein A1-Based Immunotherapeutics

In the slipstream of targeting the adaptive immune system, innate immunotherapy strategies are being developed. In this context, technologies based on natural carrier vehicles that inherently interact with the innate immune system, are increasingly being considered. Immunoregulatory nanotherapeutics based on natural apolipoprotein A1 (apoA1) are discussed here. This protein is a helical, amphipathic macromolecule and the main constituent of high-density lipoprotein. In that capacity, apoA1 interacts specifically with innate immune cells, such as monocytes and macrophages, to collect and transport lipophilicmolecules throughout the body. Exactly these unique features make apoA1 a compelling elementary constituent of biocompatible self-assembled nanotherapeutics. Such apoA1-based nanotherapeutics (A1-nanotherapeutics) can be engineered and functionalized to induce or mitigate an innate immune response or to orchestrate an adaptive immune response through antigen delivery to dendritic cells. The authors first discuss apoA1's properties and how these can be exploited to generate libraries of A1-nanotherapeutics using advanced manufacturing approaches such as microfluidics or continuous flow methods. Using high-throughput in vitro screening methods and in vivo imagingto identify promising formulations are then recommend. Finally, Three distinct immunotherapy strategies are proposed to effectively treat a variety of diseases—including cancer, infection, and cardiovascular disease—and promote allograft survival in transplantation