Current understanding of interactions between nanoparticles and the immune system

Abstract

The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure-activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle-immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15years of research on the immunotoxicity of engineered nanomaterials.

Keywords: Drug delivery; Immunology; Immunotoxicity; Nanoparticles; Preclinical.

Fig. 1

Publications statistics. The PubMed data base was searched using the keywords “nanoparticles” and “immune system” for the years 2000–2015. The data for 2015 were excluded from the analysis because the publication year was incomplete at the time of the search. Each bar shows the total publication number per year.

Fig. 2

Achievements, disappointments, and lessons learned from the characterization of engineered nanomaterials over the past decade. This diagram outlines achievements (left circle) and disappointments (right circle) based on the studies dedicated to investigating nanoparticle immunotoxicity over the past decade. The overlapping area shows the lessons learned from these studies. API- active pharmaceutical ingredient; NP – Nanoparticles; PCP – Physicochemical properties, CARPA – Complement activation-related pseudoallergy, ICH – International Conference on Harmonization.

Figure 3

Structure–activity relationship summary. Shown are the structure–activity relationships between nanoparticles and their effects on the immune system. Each block listed in the bottom (structure) part of the figure is color-coded. To find what toxicity is related to the given structure block, please find the block in the top (activity) part of the figure marked with the color matching that of the structure block. PCA – Procoagulant activity, DIC – Disseminated intravascular coagulation, CARPA – Complement activation-related pseudoallergy, MPS – Mononuclear phagocytic system, IL – Interleukin, PEG – Polyethylene glycol, NP – Nanoparticle, DXR – Doxorubicin, API – Active pharmaceutical ingredient, DNA – Deoxyribonucleic acid.