Chapter 11: Nanoparticles and Antigenicity

The immune system is highly versatile at recognizing foreign substances and mounting a multi-stage response against them. Antigenicity is a subtype of the immunogenic response characterized by the formation of an antibody specific to the given type of foreign substance, called an antigen. Due to their small size, nanoparticles are not antigenic themselves. However, some of them act as haptens and become antigenic when conjugated to a protein carrier. Antibodies against several types of engineered nanomaterials have been produced by the conjugation of the nanomaterial to a protein carrier and immunization in the presence of strong adjuvants. Conversely, engineered nanomaterials not conjugated to a protein, and those specifically designed to carry therapeutics proteins, were shown to be non-antigenic and moreover, helped to reduce the antigenicity of therapeutic proteins attached to them. However, accidental non-engineered nanomaterials which contaminate clinical formulations of therapeutic proteins are believed to contribute to their antigenicity. This chapter will review the scientific literature regarding the antigenic response to engineered nanomaterials, describe nanoparticle physicochemical properties contributing to antigenicity, with focus on the role of nanoparticle surface coating in antibody generation, and discuss the role of accidental nanoparticles in the antigenicity of therapeutic proteins.