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

ABSTRACT 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 Ce 3 + /Ce 4 + onto Fe 3 O 4 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.