Molecularly Imprinted Polymers as Interceptors of Bacterial Quorum Sensing: Design Principles, Translational...

Quorum sensing (QS) orchestrates virulence, biofilm maturation, and antimicrobial tolerance across clinically dominant pathogens, driving chronic infections and therapeutic failure. Although quorum-sensing inhibitors (QSIs) were developed to attenuate pathogenic coordination without bactericidal pressure, their clinical translation has been constrained by biochemical instability, narrow receptor specificity, limited pharmacokinetic robustness, and emerging adaptive resistance. Molecularly imprinted polymers (MIPs) provide a mechanistically distinct strategy based on structurally defined recognition cavities capable of physically sequestering or catalytically degrading autoinducers with measurable thermodynamic parameters, including the imprinting factor (IF), dissociation constant (K _d), and binding capacity. This review critically synthesizes advances in molecularly imprinted polymer design for QS detection and modulation, emphasizing the role of monomer-template complementarity, cross-link density, porogen environment, polymerization strategy, and template removal in governing recognition fidelity and biological performance. Computational modeling has improved monomer selection and prepolymerization complex prediction, yet translational reliability requires integration of solvent dynamics, cross-linker effects, and matrix competition under physiologically relevant conditions. Compared with conventional biosensors and small-molecule QSIs, MIPs demonstrate nanomolar detection limits, resilience in complex media, and up to 80% biofilm inhibition through signal sequestration. Early in vivo studies further support their potential to attenuate the QS-dependent virulence. Despite these advances, barriers remain, including monomer cytotoxicity, nonspecific adsorption in biological fluids, incomplete biodegradation profiling, and the need for standardized in vivo validation frameworks. With rational engineering and regulatory alignment, MIPs represent a programmable materials platform for communication-based infection control, expanding the antivirulence paradigm beyond receptor antagonism toward structurally resilient quorum interception.