Diosgenin Functionalized Iron Oxide Nanoparticles as Novel Nanomaterial Against Breast Cancer

Abstract

Iron oxide nanoparticles (IONPs) have gained immense importance recently as drug nanocarriers due to easy multifunctionalization, simultaneous targeting, imaging and cancer hyperthermia. Herein, we report a novel nanomedicine comprising of IONPs core functionalized with a potent anticancer bioactive principle, diosgenin from medicinal plant Dioscorea bulbifera via citric acid linker molecule. IONPs were synthesized by reverse co-precipitation and characterized using field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and dynamic light scattering (DLS). Diosgenin functionalization was confirmed using fourier transform infrared spectroscopy (FTIR) and biochemical methods. Synthesized IONPs, citrate linked IONPs (IONPs-CA), diosgenin functionalized IONPs (IONPs-D) along with free citric acid and diosgenin were checked for anticancer activity against MCF7 breast cancer cells by MTT assay, wound migration assay, confocal microscopy and protein expression by western blotting. Size of IONPs, IONPs-CA and IONPs-D gradually increased ranging from 12 to 21 nm as confirmed by FESEM and HRTEM. Signature peaks of diosgenin at 2914, 1166 and 1444 cm-1 IONPs-D, revealed in FTIR indicated the presence of functionalized diosgenin. IONPs-D exhibited 51.08 ± 0.37% antiproliferative activity against MCF7 cells, which was found to be superior to free citric acid (17.71 ± 0.58%) and diosgenin (33.31 ± 0.37%). Treatment with IONPs-D exhibited reduced wound migration upto 40.83 ± 2.91% compared to bare IONPs (89.03 ± 2.58%) and IONPs-CA (50.35 ± 0.48%). IONPs-D and diosgenin exhibited apoptosis induction, confirmed by Alexa Fluor 488 annexin V/PI double-stained cells indicating extensive cell membrane damage coupled with PI influx leading to nuclear staining in treated cells. IONPs-D mediated selective PARP cleavage strongly rationalized it as superior apoptotic inducers. Based on these findings, IONPs-D can be considered as first diosgenin functionalized novel magnetic nanomedicine with antiproliferative, migration inhibiting and apoptosis inducing properties against breast cancer.

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