Ligand Functionalization and Fe Precursor Selection Modulated the Physicochemical Properties of Fe-MOFs and Their Biological Response on Prostate Cancer and Normal Prostate Cells

Abstract Metal-organic frameworks (MOFs) offer modular platforms for cancer nanomedicine, but how metal precursor chemistry and linker functionalization jointly regulate physicochemical properties and biological response remains insufficiently defined. Here, three Fe-based MOFs, Fe-BDC-1, Fe-BDC-2, and Fe-NH2-BDC, were synthesized by solvothermal routes using BDC or NH2-BDC linkers and Fe nitrate or Fe chloride precursors. XRD, FTIR, SEM, magnetic measurements, UV–Vis diffuse reflectance, and photoluminescence analyses showed that Fe-BDC-1 and Fe-BDC-2 form closely related Fe-BDC frameworks, with FeCl3 promoting higher crystallinity and distinct particle assembly, whereas amino functionalization yields a structurally and optically distinct Fe-NH2-BDC phase with broadened visible-light absorption, lower band-gap energy, and enhanced emission. Biological activity was assessed in PC-3 prostate cancer cells and PNT1A normal prostate epithelial cells using WST-1 assays under magnet-free and magnet-exposed conditions, followed by DOX-combination testing and Annexin V/PI flow cytometry. Fe-BDC-2 displayed pronounced intrinsic toxicity toward PC-3 cells, including near-complete viability loss at 150 μg/mL after 48 h, while PNT1A cells showed comparatively lower sensitivity under selected conditions. Magnetic exposure further amplified cytotoxicity, particularly at higher doses and prolonged exposure. In WST-1 assays, Fe-NH2-BDC co-treatment with DOX produced the most consistent reduction in PC-3 metabolic viability under selected conditions. However, Annexin V/PI analysis did not indicate enhanced apoptosis and instead revealed predominantly PI-positive membrane damage with mixed cell-death features. Magnetic exposure further amplified cytotoxicity, particularly at higher doses and prolonged exposure. In WST-1 assays, Fe-NH2-BDC co-treatment with DOXorubicin (DOX) produced the most consistent reduction in PC-3 metabolic viability under selected conditions. However, Annexin V/PI analysis did not indicate enhanced apoptosis and instead revealed predominantly PI-positive membrane damage with mixed cell-death features. These findings identify linker functionalization and precursor selection as coupled design variables for tuning Fe-MOF structure, magnetoresponsive behavior, and chemotherapy-associated biological response. These findings identify linker functionalization and precursor selection as coupled design variables for tuning Fe-MOF structure, magnetoresponsive behavior, and chemotherapy-associated biological response.