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Background: Water-dispersed lanthanide coordination polymers (LCPs) have attracted considerable attention owing to their superiority in bioanalysis. However, so far, most of the reported LCPs, due to the employment of water-insoluble and toxic organic molecules as ligands, are only competent in organic solution or the gaseous phase. Therefore, the construction of a water-dispersed, LCP-based, especially LCP nanoparticle (LCPNP)-based, sensor is still lacking and challenging., Objective: The aim was to obtain a novel and effective LCPNP-based sensor for Zn2+ by simple self-assembly, utilizing water-soluble guanosine monophosphate (GMP) as ligand and Eu3+ as luminescence center, ., Methods: In aqueous solutions, Eu-GMP NPs were formed via self-assembly reaction between Eu3+ and GMP, and displayed very weak fluorescence due to low energy transfer from GMP to Eu3+ and the rate constant of nonradiactive deactivation of the excited states caused by the O-H vibration of coordinated water molecules. After the introduce of Zn2+, forming Eu-GMP/Zn, very interestingly, an 8-fold fluorescence enhancement was observed due to the removal of coordination water molecules and fluorescence sensitization of Zn2+., Results: The fluorescence intensity of Eu-GMP NPs at 614 nm showed a linear relationship with the concentration of Zn2+ from 4 to 240 μM with a detection limit of 4 μM. Due to possessing long fluorescence, Eu-GMP showed prominent achievment for application in serum Zn2+ determination., Conclusion: The LCPNP probe exhibited excellent performance for the determination of Zn2+ in serum., Highlights: For the first time, we developed and designed a kind of water-dispersed, LCPNP-based turn-on fluorescence assay for Zn2+ in serum. High sensitivity and good recoveries were achieved due to long fluorescence life, good water-dispersed behavior, and the turn-on fluorescence response of the LCPNP probe., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)