The investigation of the interaction of warangalone with transferrin as a therapeutic biological macromolecule and the formation of a protein-ligand nanocomplex with superior anticancer activity against lung cancer cells.

Though warangalone has shown anticancer properties against breast cancer cells, its colloidal stability and therapeutic index ought to be improved using a potential strategy, especially via protein-based (nano)carriers. In this research, transferrin was used as a plasma protein for the development of the warangalone-transferrin NPs. To investigate the mechanism underlying the formation of this complex, the interaction between warangalone and transferrin, as well as transferrin NPs, was analyzed using spectroscopic methods. The anticancer properties of warangalone and warangalone-transferrin NPs in lung cancer were subsequently evaluated. The findings showed that the hydrodynamic size, PDI, and zeta potential values of transferrin NPs were 122.4 ± 12.38 nm, 0.210, and -23.40 ± 3.28 mV, respectively. The association between warangalone and transferrin NP showed a strong binding strength (log K = 5.44 ± 0.07), while this affinity was reduced for the warangalone and the transferrin protein (log K = 4.88 ± 0.04). Theoretical research indicated that hydrophobic interactions serve as the main driving forces for the interaction of warangalone and transferrin. Cellular assays showed that the warangalone-transferrin NPs significantly affected cell death in lung cancer cells. This research, by offering promising data, could be highly beneficial for advancing warangalone-transferrin NPs as a promising anticancer platform.