Understanding the immunogenicity and antigenicity of nanomaterials: Past, present and future

Abstract

Nanoparticle immunogenicity and antigenicity have been under investigation for many years. During the past decade, significant progress has been made in understanding what makes a nanoparticle immunogenic, how immune cells respond to nanoparticles, what consequences of nanoparticle-specific antibody formation exist and how they challenge the application of nanoparticles for drug delivery. Moreover, it has been recognized that accidental contamination of therapeutic protein formulations with nanosized particulate materials may contribute to the immunogenicity of this type of biotechnology products. While the immunological properties of engineered nanomaterials and their application as vaccine carriers and adjuvants have been given substantial consideration in the current literature, little attention has been paid to nanoparticle immuno- and antigenicity. To fill in this gap, we herein provide an overview of this subject to highlight the current state of the field, review past and present research, and discuss future research directions.

Keywords: Anaphylaxis; Antibody; Antigenicity; Cytokines; Immunogenicity; Nanoparticles; Phagocytosis; Preclinical.

Fig. 1

Consequences of antibody response to biotechnology-based therapeutics. Antidrug antibodies (ADA) have a broad spectrum of effects, which may lead to changes in protein efficacy, possibly resulting in undesirable toxicity and clearance of the biotechnology-based product. PK – Pharmacokinetics, IFN – Interferon, IL – Interleukin.

Fig. 2

Timeline of understanding of nanoparticle antigenicity. Our understanding of nanoparticle immunogenicity has evolved from anecdotal reports describing the generation of the particle-specific antibodies to uncovering the differences between particle types, determining the roles of their physicochemical properties, and developing approaches to enhance desirable and avoid undesirable immunogenicity. Future research will focus on methodologies and mechanisms, and leveraging this knowledge for the development of safe nanomedicines. PCP – Physicochemical properties.

Fig. 3

Nanoparticle antigenicity. Current data about nanoparticles and antibody response are summarized. * – Immunization required a strong adjuvant and either conjugation to a protein carrier or the presence of a TLR agonist. ENM – Engineered nanomaterial, ThPr – Therapeutic protein; SWCNT – Single-wall carbon nanotubes, PAMAM – Polyamidoamine, PEG – Polyethylene glycol, PS – Phosphatidyl serine, TNF – Tumor necrosis factor.