Single-step preparation of Fe-doped ZnO/Fe₃O₄ nanocomposite for efficient and selective photodynamic anti-cancer applications

Photodynamic therapy (PDT) is a promising technique for cancer treatment using active and selective photosensitizer materials. In this work, we investigate the effect of varying Fe doping on ZnO host structure using systematic and comprehensive characterizations. The structural analysis confirmed that Fe successfully doped into ZnO at low concentration of 2.5 % while increasing the Fe ≥5 % formed Fe-doped ZnO/Fe₃O₄ nanocomposite. The bandgap energy also decreases from 3.17 eV (Fe-0 %) to 2.27 eV (Fe-20 %) enhanced visible-light absorption. Compared with previously reported Fe3O4 /ZnO systems, this single-step synthesized nanocomposite demonstrates improved structural uniformity and a more pronounced bandgap reduction, enabling superior visible-light activation. The results of in vitro MTT assays demonstrated that selective phototoxicity against MA-104 normal cells maintained >80 % viability under irradiation up to 200 µg/mL, whereas MDA-MB-231 cancer cells showed a sharp decline in viability with an IC₅₀ of 49.6 µg/mL for Fe-20 % under 635 nm light. Molecular docking revealed favorable interactions of the Fe-doped ZnO/Fe₃O₄ composite with apoptosis-regulating proteins (Caspase-3, BAX, and BCL-2), supporting its mechanistic role in apoptosis modulation. This represents a marked improvement in cytotoxic selectivity compared to previously reported Fe₃O₄/ZnO nanocomposites, confirming the effectiveness of the optimized Fe-doping strategy. These findings highlight Fe-doped ZnO/ Fe₃O₄ as a promising nanoplatform for efficient and selective PDT with minimized toxicity to normal cells.