biostudies-literatureUnknown14(1)Murphy KRHigh-frequency irreversible electroporation (H-FIRE), a nonthermal brain tumor ablation therapeutic, generates a central tumor ablation zone while transiently disrupting the peritumoral blood-brain barrier (BBB). We hypothesized that bystander effects of H-FIRE tumor cell ablation, mediated by small tumor-derived extracellular vesicles (sTDEV), disrupt the BBB endothelium. Monolayers of bEnd.3 cerebral endothelial cells were exposed to supernatants of H-FIRE or radiation (RT)-treated LL/2 and F98 cancer cells. Endothelial cell response was evaluated microscopically and via flow cytometry for apoptosis. sTDEV were isolated following H-FIRE and RT, characterized via nanoparticle tracking analysis (NTA) and transmission electron microscopy, and applied to a Transwell BBB endothelium model to Scientific reports28533https://www.ebi.ac.uk/biostudies/studies/S-EPMC11574144biostudies-literatureTumor-derived extracellular vesicles disrupt the blood-brain barrier endothelium following high-frequency irreversible electroporation.PMC11574144Aycock KNAthanasiadi IBracha SMarsh SMurphy KRRossmeisl JHDervisis NGHay ANChang CGourdie RDavalos RVfalseTumor-derived extracellular vesicles disrupt the blood-brain barrier endothelium following high-frequency irreversible electroporation.High-frequency irreversible electroporation (H-FIRE), a nonthermal brain tumor ablation therapeutic, generates a central tumor ablation zone while transiently disrupting the peritumoral blood-brain barrier (BBB). We hypothesized that bystander effects of H-FIRE tumor cell ablation, mediated by small tumor-derived extracellular vesicles (sTDEV), disrupt the BBB endothelium. Monolayers of bEnd.3 cerebral endothelial cells were exposed to supernatants of H-FIRE or radiation (RT)-treated LL/2 and F98 cancer cells. Endothelial cell response was evaluated microscopically and via flow cytometry for apoptosis. sTDEV were isolated following H-FIRE and RT, characterized via nanoparticle tracking analysis (NTA) and transmission electron microscopy, and applied to a Transwell BBB endothelium model to 2024-01-01T00:00:00Z2024 Nov2026-07-17T00:01:55.513Z2025-04-05T19:58:41.22ZS-EPMC115741443955795910.1038/s41598-024-79019-5