Profiling and Regulating Proteins That Adsorb to DNA Materials in Human Serum.

DNA aptamers and framework DNA nanostructures are emerging DNA materials with many appealing biological applications including biosensing, bioimaging, drug delivery, and so forth. When placed in physiological fluids, they inevitably encounter biomolecules (majorly proteins) and form complexes that largely affect their biological fate. Nevertheless, little is known regarding the quantitative profile of proteins that adsorb to DNA aptamers and DNA nanostructures in biological environments, and there are no potent strategies to regulate protein profiles. Herein, we performed a proteomic analysis to profile proteins that bind to DNA aptamers (Sgc8c and SYLC3) and nanostructures (a tetrahedral DNA nanostructure and a DNA origami rod) in human serum using liquid chromatography-mass spectrometry (LC-MS). Dozens to hundreds of proteins were identified with each DNA material exhibiting highly distinctive profiles. It was also revealed that the origin of serum (from healthy donor vs from prostate cancer patients) causes significant differences in profiles of bound proteins. Furthermore, we demonstrated that the protein profile may be regulated by tethering a layer of single-stranded DNA (polythymine) onto the DNA origami rod to alleviate the adsorption of complement-associated proteins, which significantly reduced its sequestration by macrophages. Taken together, this study has provided qualitative and quantitative proteomic profiles regarding serum proteins that adsorb to various DNA materials and have demonstrated that the composition of interacted proteins may be regulated toward better biological performances.