Yolk–shell magnetic mesoporous TiO2 microspheres with flowerlike NiO nanosheets for highly selective enrichment of phosphopeptides

Abstract

In this work, we fabricated a yolk–shell magnetic composite that contains mesoporous TiO₂ as the inner shell and flowerlike NiO as the outer shell (denoted as Fe₃O₄@H-TiO₂@f-NiO) to reduce the limitations of single-component metal oxides in phosphopeptide enrichment. The NiO nanosheets play a synergistic role in phosphopeptide enrichment. And the unique flowerlike structure of NiO with sufficient space can facilitate the reversible insertion/extraction of peptides, which will have less impact on the enrichment process of the inner TiO₂ shell. The yolk–shell structure and two types of porous nanostructures endowed this composite with a high surface area (156.58 m² g⁻¹) and a large pore volume (0.37 cm³ g⁻¹). Owing to the high surface area and combined properties of TiO₂ and NiO, the Fe₃O₄@H-TiO₂@f-NiO microspheres showed a better performance for phosphopeptide enrichment than the same material without NiO nanosheets (Fe₃O₄@H-TiO₂). According to the LC-MS/MS results, 972 unique phosphopeptides were identified from HeLa cell extracts with a high selectivity (91.9%) by Fe₃O₄@H-TiO₂@f-NiO relative to 837 phosphopeptides (selectivity: 60.2%) by Fe₃O₄@H-TiO₂. The results demonstrated that, compared with single-component metal oxides, composite metal oxides could enhance the selectivity and sensitivity for phosphopeptide enrichment.