The ancillary effects of nanoparticles and their implications for nanomedicine

Nanoparticles are often engineered as a scaffolding system to combine targeting, imaging and/or therapeutic moieties into a unitary agent. However, mostly overlooked, the nanomaterial itself interacts with biological systems exclusive of application-specific particle functionalization. This nanoparticle biointerface has been found to elicit specific biological effects, which we term ‘ancillary effects’. In this Review, we describe the current state of knowledge of nanobiology gleaned from existing studies of ancillary effects with the objectives to describe the potential of nanoparticles to modulate biological effects independently of any engineered function; evaluate how these effects might be relevant for nanomedicine design and functional considerations, particularly how they might be useful to inform clinical decision-making; identify potential clinical harm that arises from adverse nanoparticle interactions with biology; and, finally, highlight the current lack of knowledge in this area as both a barrier and an incentive to the further development of nanomedicine. Nanoparticles used for biomedical applications might elicit unexpected adverse or beneficial biological effects unrelated to the function for which they were designed. In this Review, the authors describe some of these ‘yin and yang’ ancillary effects, and discuss their implications for nanomedicine development.