Nanoengineering Apolipoprotein A1‐Based Immunotherapeutics

• Published in: Advanced therapeutics 2021-08, Vol.4 (8), p.n/a
• Main Authors: Schrijver, David P., Dreu, Anne, Hofstraat, Stijn R. J., Kluza, Ewelina, Zwolsman, Robby, Deckers, Jeroen, Anbergen, Tom, Bruin, Koen, Trines, Mirre M., Nugraha, Eveline G., Ummels, Floor, Röring, Rutger J., Beldman, Thijs J., Teunissen, Abraham J. P., Fayad, Zahi A., Meel, Roy, Mulder, Willem J. M.
• Format: Article
• Language: English
• Subjects: apolipoprotein A1; immunoengineering; immunotherapy; nanomedicine; nanotherapeutics; trained immunity
• ISSN: 2366-3987; 2366-3987
• DOI: 10.1002/adtp.202100083

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 lipophilic molecules 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 imaging to 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. While conventional nanomedicines are designed to evade the mononuclear phagocyte system, nanotherapeutics based on apolipoprotein A1 (A1‐nanotherapeutics) deliberately engage myeloid cells to induce or mitigate a specific immune response. In this review, the engineering and characteristics of A1‐nanotherapeutics are summarized, and their potential for treating immune‐mediated diseases is discussed.