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 metalmediated 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 <1 nM target DNA was achieved in serum and other biological samples, and imaging of cancer-related microRNA in cells was demonstrated. The DNA binding mechanism on PDAN was further studied by ligand displacement experiments and X-ray photoelectron spectroscopy characterization, which demonstrated the critical role of polyvalent metal ions to bridge DNA with PDANs. This work provides fundamental insights into the biointerface science of PDANs with DNA, which can benefit applications in biosensor design, directed assembly of nanomaterials, bioimaging, and drug delivery.