Targeted immunomodulation using antigen‐conjugated nanoparticles

Abstract

The growing prevalence of nanotechnology in the fields of biology, medicine and the pharmaceutical industry is confounded by the relatively small amount of data on the impact of these materials on the immune system. In addition to concerns surrounding the potential toxicity of nanoparticle (NP)-based delivery systems, there is also a demand for a better understanding of the mechanisms governing interactions of NPs with the immune system. Nanoparticles can be tailored to suppress, enhance, or subvert recognition by the immune system. This “targeted immunomodulation” can be achieved by delivery of unmodified particles, or by modifying particles to deliver drugs, proteins/peptides or genes to a specific site. In order to elicit the desired, beneficial immune response, considerations should be made at every step of the design process: the NP platform itself, ligands and other modifiers, the delivery route, and the immune cells that will encounter the conjugated NPs can all impact host immune responses.

Tolerogenic Nanoparticles to Treat Islet Autoimmunity

“…Smaller particles (< 100–200 nm) drain there freely. Larger particles (> 100–200 nm) must be transported there by APCs [4, 5•, 68, 69]. Particles less than 30 nm seem to be able to escape the lymph node once there [70].…”

“…Nanoparticle charge can be influenced by surfactants and other coating materials, thereby allowing manipulation of their interaction with the immune system [4]. Cationic particles are more likely to elicit a Th1 response, be taken up by dendritic cells, and engage the MHC class I loading pathway following phagocytosis [4, 74–78], but they have also potentially toxic properties [79, 80].…”

“…Cationic particles are more likely to elicit a Th1 response, be taken up by dendritic cells, and engage the MHC class I loading pathway following phagocytosis [4, 74–78], but they have also potentially toxic properties [79, 80]. Conversely, anionic particles exhibit low toxicity in a number of studies [81–86] and associate with the macrophage scavenger receptor MARCO favoring tolerance induction [4, 87]. …”

“…Nanotechnology as a concept has been in existence for approximately 60 years, but its application to medical therapy dates back about half that time [4, 5•]. While nanomedicine may have a multitude of incarnations ranging from diagnostic devices to tissue regeneration, much of it has focused on the reformulation and delivery of small molecules or biologic drugs such as proteins or nucleic acids [2, 4, 5•].…”

“…While nanomedicine may have a multitude of incarnations ranging from diagnostic devices to tissue regeneration, much of it has focused on the reformulation and delivery of small molecules or biologic drugs such as proteins or nucleic acids [2, 4, 5•]. More recently, researchers have turned to nanoparticles for immunomodulation and as potential therapeutics for immune-related diseases [4, 5•, 6]. The end goal of many of these new approaches is to reestablish immune tolerance.…”