工程化细胞外囊泡递送AZD5582致敏TRAIL应答治疗乳腺癌研究

riple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by the lack of effective targeted therapies leading to drug resistance. Research indicates that Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) holds potential anti-cancer effects on cancer cells; however, clinical trials with recombinant TRAIL (rTRAIL) have failed due to widespread TRAIL resistance in cancer. Studies have shown that extracellular vesicle-mediated TRAIL delivery (EV-T) significantly enhances cytotoxicity. AZD5582 (AZD), as a Smac mimetic, acts as an inhibitor of IAPs, sensitizing TRAIL responses. The study hypothesized encapsulating AZD within EV-T to develop an efficient composite nano-drug for treating TNBC. Results demonstrate that AZD@EV-T effectively overcomes TRAIL resistance, enhances TNBC cell apoptosis, leading to complete tumor regression, possibly through the downregulation of anti-apoptotic factors (cFLIP, MCL-1, BCL-2, and Survivin). In conclusion, the AZD5582@EV-T nano-composite formulation exhibits the potential to overcome TRAIL resistance, offering a novel strategy for treating triple-negative breast cancer.