Multifunctional coumarin-functionalized 5-HT₇ receptor–targeted MOF nanocarriers for epilepsy-related neuroprotection via regulation of NMDAR/GABAR balance

Small exogenous molecules widely present in the environment not only pose risks to food safety but may also contribute to the development of neurological disorders by disrupting the excitatory–inhibitory balance of the central nervous system. To achieve multifunctional applications of natural-product-based materials, this study employed the coumarin derivative Coumarin-OH, extracted from
Angelica dahurica
, as a functional modifier to construct a surface-engineered CP1-based metal–organic framework (MOF), yielding the Coumarin-OH@CP1 composite. Further loading of the 5-HT₇ receptor agonist AS19 resulted in the formation of the Coumarin-OH@CP1@AS19 nanosystem (
AS19-NPs
). Comprehensive characterization revealed that the composite possessed well-defined porosity, tunable interfacial charge properties, and stable electrochemical responsiveness. Leveraging these features, the developed electrochemical sensing platform enabled sensitive detection of the phthalate contaminant diethyl phthalate (DAP), demonstrating a wide linear range and excellent anti-interference performance. In the neuroprotection studies,
AS19-NPs
significantly improved the viability of glutamate-injured HT22 cells and effectively reversed the transcriptional imbalance characterized by upregulation of N-methyl-D-aspartate receptor (NMDAR) subunits (Grin1, Grin2a) and downregulation of the γ-gamma-aminobutyric acid receptor (GABAR) subunit (Gabra1). The neuroprotective efficacy of
AS19-NPs
was markedly superior to that of free AS19. Overall, this work highlights the dual application potential of natural-product-functionalized MOF materials in both food safety monitoring and intervention of neurological disorders, offering a promising strategy for the development of multifunctional nanoplatforms.