Resveratrol-loaded magnetic molecularly imprinted polymers: a green dual-functional platform for synergistic antibacterial and targeted anticancer therapy

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Abstract Background Resveratrol (RSV) is a natural polyphenol with potent antimicrobial and anticancer activities. However, its biomedical applications are limited by its poor solubility, instability, and lack of targeted delivery systems. Smart carriers are needed to enhance RSV efficacy, selectivity, and safety. Method An innovative magnetic molecularly imprinted polymer (MMIP-RSV) for the selective binding of resveratrol was prepared by embedding Fe 3 O 4 nanoparticles into a chitosan–poly(cyclodextrin-citrate) polymer matrix. The polymer was characterized by FT-IR, UV–Vis, TEM, and zeta potential analysis, and Adsorption capacity, kinetics, selectivity, and reusability were assessed. Antimicrobial efficacy was assessed via MIC and MBC against five multidrug-resistant strains, and anticancer activity was evaluated on Caco-2 and MCF-7 cells, with HFB-4 fibroblasts as normal controls. Results The MMIP-RSV platform enabled both extraction and nanoformulation of resveratrol in a single step. MMIP-RSV achieved a high adsorption capacity (129.6 ± 1.2 mg/g), a 6.6-fold improvement, with qRSV = 25.6 ± 0.90 µg/mg, IF = 2.88, selectivity factor αRSV = 2.81, indicating 125% enhanced target selectivity. Reusability tests showed >97% capacity retention over five cycles, declining to 82.8% after six cycles. Antimicrobial activity: MMIP-RSV significantly enhanced RSV potency with MIC reductions of ~77% against MRSA ( Methicillin - resistant Staphylococcus aureus), Enterococcus faecalis , and Salmonella Typhi . The inhibition zones were 26.0 ± 1.15 mm for S . aureus and 27.0 ± 0.58 mm for E. faecalis , compared to gentamicin (1mg /mL), outperforming free RSV. Gram-negative bacteria exhibited moderate improvement. Anticancer activity: MMIP-RSV selectively inhibited Caco-2 cells (IC 50 = 26 µg/mL RSV-equivalent), demonstrating enhanced cytotoxic efficacy compared to free RSV. While free RSV maintained >80% viability in normal HFB-4 fibroblasts even at 1000 µg/mL, MMIP-RSV exhibited a higher selectivity index (6.07 vs. 1.04 for free RSV), although some reduction in fibroblast viability was observed at high total formulation concentrations. Conclusion This study successfully developed a novel, eco-friendly MMIP (magnetic molecularly imprinted polymer) via a simple one-pot synthesis for the highly selective extraction and delivery of resveratrol. The remarkable binding capacity, selectivity, and enhanced therapeutic efficacy demonstrated in this study position the MMIP-RSV system as a robust and sustainable strategy with significant potential for applications in targeted drug delivery, nutraceutical purification, and advanced biomedical therapies. Graphical abstract

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