Green synthesis of folic acid-functionalized Fe3O4 nanoparticles using kepok banana peel: in vitro and in silico studies toward FR-positive cancer target

Iron oxide nanoparticles possess great potential as T₂ magnetic resonance imaging contrast agents due to their ability to enhance image contrast and sensitivity. In this study, Fe₃O₄ nanoparticles were synthesized via a green coprecipitation method using banana Musa x paradisiaca L. peel extract as a natural reducing agent, followed by surface functionalization with PEG–APTMS–FA through the EDC/NHS coupling method. Nanoparticles were functionalized with folic acid (FA) to enable specific targeting of cancer cells by selectively binding to the overexpressed folate receptors on the surface of cervical cancer cells. Characterization results revealed spherical morphology with a cubic spinel magnetite structure. The particle size decreased from 704.9 nm to 266 nm after functionalization, while a zeta potential of −34.4 mV indicated good colloidal stability. FTIR and UV-Vis analyses confirmed successful FA conjugation through the appearance of amide bands and characteristic absorption peaks at 287 and 358 nm. TEM analysis showed particle core sizes of 25–45 nm, and SAED analysis confirmed the Fe₃O₄ structure (JCPDS 88-0315). Molecular docking analysis with AutoDock 4 revealed a strong binding energy of −7.72 kcal/mol with the folate-α receptor, while in vitro assays demonstrated that in the KB cell line, after treatment, viability remained 90%, and cellular internalization was 22-fold increased. Overall, the green-synthesized Fe₃O₄–APTMS–PEG–FA nanoparticles exhibit stable physicochemical properties, biocompatibility, and strong receptor-targeting capability, making them promising candidates for targeted MRI contrast agents.