Abstract
White mulberry leaf nanoemulsion (WML-NE) showed much higher antiproliferative activity against human breast cancer MCF-7 cells than a fruit-based nanoemulsion (WM-NE). After 48 h of exposure, WML-NE had only half the IC₅₀ value (14.52 µg/mL) compared to that of WM-NE (29.23 µg/mL), which means that WML-NE was almost twice as potent cytotoxic. The inclusion of nanoformulations in the experiment led to a significant decrease in the number of living cells, the appearance of apoptosis, and the halt of the cell cycle at phase G0/G1, thus, the anticancer agents might be involved in the execution of programmed cell death and growth inhibition pathways. Breast cancer is still one of the main causes of death from cancer all over the globe, this fact pointing out the requirement for new therapeutic approaches that are safe, effective, and of natural origin. Morus alba, a plant rich in flavonoids, phenolic acids, and other phytochemicals, is a good source of health-beneficial bioactive agents. Loading these substances into nanoemulsion delivery systems improves their solubility, stability, and uptake by cells, thereby intensifying their pharmacological activity. Overall, this research lays the groundwork for utilizing mulberry leaves as a novel plant-based nanotherapeutic agent with the highest efficiency. Accordingly, these findings can be used to propose the application of mulberry-derived nanoemulsions as auxiliary or alternative methods in breast cancer treatment and, thus, further in vitro and in vivo studies can contribute to their validation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-29733-5.