Hierarchically Porous MOF Shell Nanoengineered on Magnetic Cores as a Nanoplatform Towards Serum Glycopeptide Decoding.

Hierarchically porous metal-organic frameworks (MOFs) offer promising potential for nano-separation, yet the controlled epitaxial growth of an ordered hierarchical porous MOF shell on heterogeneous cores remains challenging due to template disruption by heterogeneous surfaces. Herein, we report a microemulsion-mediated in situ growth strategy to construct a magnetic core-shell structure with a well-ordered hierarchically porous MOF shell (denoted as FeM@PMOFs). Mercaptoacetic acid (MAA) serves as a molecular bridge to anchor Ce3 +/Ce4 + onto Fe3O4 surfaces, while a P123/mesitylene soft-template system guides the formation of hierarchical porosity. FeM@PMOFs exhibit uniform morphology, a shell thickness of about 46 nm, and hierarchical pore sizes (9-68 nm meso/macropores together with 1.58 nm micropores). Leveraging hierarchically porous, excellent hydrophilicity owing to the MOF shells, and rapid magnetic separation, FeM@PMOFs enable selective and sensitive enrichment of N-glycopeptides with an exceptionally low detection limit of 1 amol µL-1. When applied to human serum samples from healthy controls and patients with prostate, bladder, and renal cancers, the platform identified 324 unique N-glycopeptides and revealed 20 candidate glycopeptide signatures distinguishing different urological malignancies. This work provides a generalizable synthetic strategy for ordered magnetic hierarchical MOF core-shell structures and establishes a versatile nanoplatform for deep glycomics analysis in complex biological fluids.