Biogenic reduction mechanisms in iron oxide nanoparticle synthesis: Strategies to mitigate microbial resistance

Antimicrobial resistance (AMR) has emerged as a major global health challenge, contributing to nearly 5 million deaths annually, according to recent WHO reports. Nanotechnology offers an alternative, with biologically produced nanoparticles being regarded as sustainable and potent antimicrobial agents. Iron oxide nanoparticles (IONPs), particularly Fe₃O₄ and Fe₂O₃, are of particular interest due to their unique magnetic, physicochemical, and bio-functional properties. The review discusses the reduction mechanism that explains the biological production of IONPs using microbial biomolecules and phytochemicals as natural capping, stabilizing, and reducing agents. Particular attention is given to biomolecules-mediated electron transfer, Fe²⁺ and Fe³⁺ redox cycling during the nucleation process and how surface functionalization determines nanoparticles' stability and activity. Additionally, this review discussed how these reduction mechanisms directly affect antimicrobial action through the generation of reactive oxygen species (ROS), membrane rupture, DNA/protein damage, and biofilm inhibition. A comparative analysis of plant and microbe-mediated synthesis is presented, along with structure-activity correlates that regulate antibacterial activity. Applications of biogenic IONPs are examined in the realms of biomedicine, industry, and the environment, with particular focus on their potential use in combination therapy to prevent antibiotic resistance. The positive factors of eco-friendliness, increased biocompatibility and multifunctionality are offset by such factors as variability in synthesis, scaling and long-term safety. Finally, in the future, the combination of clinical translation regulatory frameworks, omics-based mapping of bacterial responses, and molecular-level mechanistic investigations will be of relative importance. Altogether, biologically synthesized IONPs are an eco-friendly and effective approach to prevent microbial resistance that can be applied to the interface between green chemistry and more sophisticated nanomedicine. This review uniquely integrates comparative plant- and microbial-mediated synthesis, mechanistic Fe³⁺/Fe²⁺ reduction pathways, physicochemical optimization parameters, and molecular antimicrobial mechanisms involved in combating multidrug-resistant pathogens.