Milk protein inspired multifunctional magnetic carrier targeting progesterone receptors: Improved anticancer potential of soybean-derived genistein against breast and ovarian cancers

Abstract

Plant-based bioactive compounds are actively researched as bioinspired green cytotoxic agents replacing synthetic drugs. The present study reports application of milk protein (casein) based pH and magnetic field responsive carrier functionalized with progesterone for the cancer site specific delivery of bioinspired cytotoxic agent genistein. Casein on hybridization with superparamagnetic calcium ferrite exhibited enhanced stability, cytocompatibility, high surface area for drug encapsulation and magnetically controllable release properties. The dietary isoflavonoid genistein was derived from soybeans using microwave-assisted method and the drug-encapsulated carrier was conjugated with progesterone to target the receptors expressed on breast or ovarian cancer cells. The drug loading in carrier was optimized to 88.67%, with a surface charge of −32.4 ± 1.6 mV and particle size 145 ± 3.7 nm. The encapsulated drug was actively released from the carrier in response to the acidic pH mimicking cancer environment (~5.4), whereas it was highly stable with negligible release at normal bodily pH (~7.4). Cell metabolic activity studies on fibroblast cells validated the non-toxicity of the system. From the selective cellular uptake and targeted chemo-hormonal effect supported by the nanocarrier, the genistein drug exhibited excellent therapeutic effect on ovarian (SKOV-3) and breast (MDA-MB-231) cancer cells, with drastic decrease in IC50 values (38.42 to 0.27 and 34.78 to 0.52 (μg/ml), respectively). The obtained results support the potential of the bioinspired, nanohybrid drug delivery system for targeted anti-cancer therapy.