ZnO-based nanostructures at the biological interface: a review of bioreceptor coupling for healthcare diagnostics and therapeutics

Zinc oxide (ZnO) nanostructures are a highly versatile class of solid-state materials with functional utility in bio-interfacial architectures, governed by the coordination chemistry of surface Zn(II) sites. Bridging the gap between inorganic nanoplatforms and complex biological environments requires a sophisticated understanding of the coordination spheres, ligand-exchange dynamics, and interfacial bonding mechanisms at the bio-nano boundary. This review provides a comprehensive, critical evaluation of the coordination ligand chemistry that has driven ZnO surface functionalization over the last decade. We systematically analyze the chemisorption and physisorption paradigms of diverse biomolecular ligands-including amino acid sequences in peptides and proteins, thiol-bearing groups, and phosphate backbones in nucleic acids, as well as functional groups in small-molecule drugs and correlate the resulting coordination modes to explore surface-ligand chemistry, stability, and molecular recognition efficiency. Furthermore, we dissect the coordination mechanics underlying targeted therapeutic delivery, oncology-driven engineering, and antimicrobial action. By offering a molecular-level perspective on ligand-surface interactions, this review outlines the coordination-chemistry principles indispensable to designing next-generation, stable bioinorganic hybrids.