A Poly(methacrolein-co-methacrylamide)-Based Template Anchoring Strategy for the Synthesis of Fluorescent Molecularly Imprinted Polymer Nanoparticles for Highly Selective Serotonin Sensing

Neurotransmitters such as serotonin regulate key physiological and cognitive functions, yet real-time detection remains challenging due to the limitations of conventional techniques like amperometry and microdialysis. Fluorescent molecularly imprinted polymer nanoparticles (fMIP-NPs) offer a promising alternative and are typically synthesized via solid-phase synthesis, in which template molecules are covalently immobilized on a solid support to enable site-specific imprinting. However, strong template-template interactions during this process can compromise selectivity. To overcome this, we incorporated a poly(methacrolein-<i>co</i>-methacrylamide)-based template anchoring strategy to minimize undesired template interactions and enhance imprinting efficiency. We optimized the synthesis of poly(methacrolein-<i>co</i>-methacrylamide) under three different conditions by varying the monomer compositions and reaction parameters. The poly(methacrolein-<i>co</i>-methacrylamide) synthesized under Condition 3 (5:1 methacrolein-to-methacrylamide molar ratio, 1:150 initiator-to-total monomer ratio, and 4.59 M total monomer concentration) yielded the most selective fMIP-NPs, whose fluorescence intensity increased with an increase in serotonin concentration, rising by up to 37% upon serotonin binding. This improvement is attributed to higher aldehyde functionality in the poly(methacrolein-<i>co</i>-methacrylamide) which enhances template immobilization and generates a rigid imprinted cavity to interact with serotonin. These findings suggest that the developed fMIP-NPs hold significant potential as imaging probes for neurotransmitter detection, contributing to advanced studies in neural network analysis.