Preadsorbed\nParticles with Cross-Shaped DNA Scaffolds\nEnable Spherical Nucleic Acid to Directly Respond to Protein in Complex\nMatrices

Spherical nucleic acids (SNAs) usually suffer from an\nundesired\nprotein corona and disrupt the function of nucleic acids (e.g., aptamer),\nthereby compromising recognition and response to proteins in the biological\nenvironment. To overcome the unexpected protein interference, specific\nproteins were initially adsorbed onto magnetic particles (MPs) as\na customized protein corona “shield” with fabricated\nnucleic acid scaffolds, forming a preadsorbed particle-based spherical\nnucleic acid (pap-SNA). By comparing with AuNPs-SNA or COOH-MPs, it\nwas found that such a protein corona “shield” of pap-SNA\nsignificantly eliminated the adsorption of nonspecific proteins or\nother biomolecules onto the MPs’ interface, thereby enabling\nthe SNA to directly respond to proteins in complex matrices. To further\nreduce the interference of protein on SNA performance, a series of\nnucleic acid scaffolds (Z-type, dsDNA type, circle type, T-type, and\ncross-shaped type) were designed by changing the rigidity and thermal\nstability of functional nucleic acids on the MPs. As a consequence,\nthe pap-SNA with a cross-shaped scaffold improved the sensitivity\nof the pap-SNA-based detection platform in that the orderly arrangement\nof functional nucleic acids provides a steric hindrance to interferents.\nMoreover, the presence of the cross-shaped scaffold not only enables\npap-SNA to exhibit a proportional response to varied protein concentrations\nbut also enhances the detection sensitivity of pap-SNA by 160% in\nserum and by 190% in urine. Therefore, incorporating optimized DNA\nscaffolds maintained and facilitated the function of a probe (aptamer)\non the surface of SNA. This approach offers a pathway for creating\nSNA with direct response and anti-interference capability applicable\nto detecting diverse biomolecules such as nucleic acids and proteins\nin biological matrices.