This work presents the use of photoactive molecularly imprinted nanoparticles (MINs) to promote antibiotic degradation under visible light irradiation. Prototype MINs for the model antibiotic tetracycline (TC) were developed using molecular dynamics simulations to predict the TC-binding capacity of seven pre-polymerization mixtures. The studied formulations contained varying proportions of functional monomers with diverse physicochemical profiles, namely N-isopropylacrylamide (NIPAM), N-tert-butylacrylamide (TBAM), acrylic acid (AA), and (N-(3-aminopropyl)methacrylamide hydrochloride) (APMA) and a constant ratio of the cross-linker N,N '-methylene-bis-acrylamide (BIS). Two monomer formulations showed markedly higher TC-binding capacities based on template-monomer interaction energies. These mixtures were used to synthesize photoactive MINs by high-dilution radical polymerization, followed by the EDC/NHS conjugation with the organic photosensitizer toluidine blue. MINs showed higher TC-binding capacities than non-imprinted nanoparticles (nINs) of identical composition. MINs and nINs exhibited photodynamic activity under visible light irradiation, as confirmed by singlet oxygen generation experiments. TC degradation was evaluated in 50 mu mol L-1 solutions placed in microplate wells containing immobilized nanoparticles and irradiated with white LED light (150 W m(-2)) for 1 h at room temperature. Degradation followed pseudo-zero-order kinetics with accelerated profiles in MIN-containing wells. Our findings suggest a key role of molecularly imprinted cavities in bringing TC closer to the photosensitizing moieties, minimizing the loss of oxidative potential due to reactive oxygen species diffusion. This degradation strategy can potentially extend to any organic pollutants for which MINs can be synthesized and opens valuable opportunities for exploring novel applications for molecularly imprinted materials.