We argue that the biological recognition of bionanoconstructs is modulated not only by their molecular composition but also by the collective architecture presented upon their surface, and we discuss fundamental aspects of this surface architecture that are central to successful recognition, such as the mode of biomolecule conjugation and nanomaterial passivation. In this review, we highlight fundamental obstacles in designing a successful bionanoconstruct, considering findings in the field of bionanointeractions.

However, the development of bionanoconstructs for the active targeting of cells and cellular compartments, both in vitro and in vivo, is challenged by the lack of understanding of the mechanisms governing nanoscale recognition. The progress achieved over the last three decades in the field of bioconjugation has enabled the preparation of sophisticated nanomaterial–biomolecule conjugates, referred to herein as bionanoconstructs, for a multitude of applications including biosensing, diagnostics, and therapeutics.

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