Nanotechnology has a great potential to revolutionize the landscape of medicine, but an inadequate understanding of the nanomaterial-biological (nano-bio) interface hampers its ultimate clinical translation. Surface attachment of biomolecules provides a new biological identity of nanoparticles that plays a crucial role in vivo as it can activate the immune system triggering inflammatory responses, clearance from the body, and cellular toxicity. In this review, we summarize and critically analyze progress in understanding the relationship between the biological identity of nanoparticles and immune system activation. Accordingly, we discuss the implications of biomolecular corona on nanotoxicity, immune safety, and biocompatibility. We also highlight a perspective on engineering the biological identity of nanoparticles for modulating immunological responses.
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