Bioorthogonal DNA Adsorption on Polydopamine Nanoparticles Mediated by Metal Coordination for Highly Robust Sensing in Serum and Living Cells

DNA-functionalized nanomaterials, such as various 2D materials, metal oxides, and gold nanoparticles, have been extensively explored as biosensors. However, their practical applications for selective sensing and imaging in biological samples remain challenging due to interference from the sample matrix. Bioorthogonal chemistry has allowed specific reactions in cells, and we want to employ this concept to design nanomaterials that can selectively adsorb DNA but not proteins or other abundant biomolecules. In this work, DNA oligonucleotides were found to be adsorbed on polydopamine nanoparticles (PDANs) via polyvalent metal-mediated coordination, and such adsorption bioorthogonally resisted DNA displacement by various biological ligands, showing better performance compared to graphene oxide and metal oxide nanoparticles for DNA detection. Using DNA/PDANs as biosensors, a detection limit of