Randomized trial demonstrates enhanced tumor suppression in HER2-positive breast cancer using EV-mediated drug delivery, suggesting an effective therapeutic strategy.
Key Points
The study aims to enhance tumor specificity and induce apoptosis in HER2-positive breast cancer cells using engineered extracellular vesicles loaded with doxorubicin.
Engineered extracellular vesicles (P51-EVDox) were created by transient transfection of HEK-293 cells with HER2-binding peptide and loaded with doxorubicin.
Antitumor efficacy was evaluated in vitro and in vivo on HER2-overexpressing BT-474 breast cancer cells.
RNA sequencing and protein analyses were conducted to investigate apoptotic mechanisms, focusing on biomarkers like cleaved caspase-3 and TXNIP activation.
P51-EVDox showed increased binding and accumulation in HER2-positive cells compared to non-targeted EV-Dox.
Transcriptomic analysis indicated significant upregulation of thioredoxin-interacting protein (TXNIP) after treatment with P51-EVDox.
Elevated levels of apoptosis markers, including cleaved caspase-3 and PARP, were observed, suggesting a ROS/TXNIP-driven apoptotic process.