Photoactivated Hypericum perforatum-derived exosomes like nanovesicles miR172 inhibits breast cancer progression by targeting CD24

Hypericum perforatum is rich in photosensitive compounds, including hypericin and pseudohypericin, known for their ability to generate reactive oxygen species (ROS) upon light activation. These ROS can induce apoptosis in cancer cells and modulate cellular signaling pathways. By incorporating these properties into exosome-like nanovesicles, photodynamic effects can be harnessed to enhance therapeutic efficacy, particularly for targeting breast cancer cells. Here we show that light treatment altered the miRNA profile of hypericum perforatum-derived exosomes-like nanovesicles (HPDENs). Exosomal nta-miR-172f was dominantly upregulated by light treatment, and could bind to the human/mouse CD24 mRNA, an innate immune checkpoint in breast cancer. Coculture of light-treated HPDENs inhibited CD24 expression in beast cancer cells compared with non-lighted HPDENs. These results demonstrate for the first time that photoactivation is a valuable approach to enhance the functionality of photosensitive plant-derived exosomes-like nanovesicles, and miRNA may represent a potential therapeutic target for breast cancer.