Low-intensity pulsed ultrasound-mediated nose-to-brain co-delivery of β-blockers and aPD-L1 enhances glioblastoma immunotherapy.
L, D., Z, Y., L, G., Y, L., Y, Z., Y, Z., M, L., L, Y., X, Y., & J, Y. (2026). Low-intensity pulsed ultrasound-mediated nose-to-brain co-delivery of β-blockers and aPD-L1 enhances glioblastoma immunotherapy.. Nature communications. https://doi.org/10.1038/s41467-026-76103-4
L D, Z Y, L G, Y L, Y Z, Y Z, et al. Low-intensity pulsed ultrasound-mediated nose-to-brain co-delivery of β-blockers and aPD-L1 enhances glioblastoma immunotherapy.. Nature communications. 2026; doi: 10.1038/s41467-026-76103-4
L D, Z Y, L G, et al. Low-intensity pulsed ultrasound-mediated nose-to-brain co-delivery of β-blockers and aPD-L1 enhances glioblastoma immunotherapy.[J]. Nature communications. 2026. DOI: 10.1038/s41467-026-76103-4.
@article{l2026,
author = {Dong L and Yun Z and Gao L and Li Y and Zhou Y and Zhu Y and Li M and Ying L and Yang X and Yue J},
title = {Low-intensity pulsed ultrasound-mediated nose-to-brain co-delivery of β-blockers and aPD-L1 enhances glioblastoma immunotherapy.},
journal = {Nature communications},
year = {2026},
doi = {10.1038/s41467-026-76103-4},
note = {PMID: 42669690},
}
TY - JOUR AU - Dong L AU - Yun Z AU - Gao L AU - Li Y AU - Zhou Y AU - Zhu Y AU - Li M AU - Ying L AU - Yang X AU - Yue J TI - Low-intensity pulsed ultrasound-mediated nose-to-brain co-delivery of β-blockers and aPD-L1 enhances glioblastoma immunotherapy. T2 - Nature communications PY - 2026 DO - 10.1038/s41467-026-76103-4 AN - PMID:42669690 ER -
Intranasal delivery offers a direct route to the brain, circumventing the blood-brain barrier (BBB) and minimizing systemic toxicity. However, its efficiency is mainly limited by the nasal mucosal barrier (NMB). Here, low-intensity pulsed ultrasound (LIPUS) without depending on the microbubbles (MBs) to amplify energy, is directly used to reversibly open the NMB by disrupting tight junction proteins. A bionic nanovesicle (iRGD-anti-programmed cell death ligand 1 (aPD-L1) & carvedilol (β-blocker) @ macrophage-derived extracellular vesicles, iMPC) is designed to co-deliver carvedilol for β-receptor blockade to reduce T-cell exhaustion, and aPD-L1 to enhance T-cell anti-tumor activity in orthotopic glioblastoma (GBM) mice during the two-hour window for NMB opening. Consequently, compared to free aPD-L1, up to a 33.38-fold increase of aPD-L1 in the GBM region is obtained with LIPUS-mediated intranasal delivery of iMPC. Reactivating T cells significantly enhances immunotherapy, leading to a 40% tumor reduction, extended survival, and long-term immune memory in orthotopic GBM mice. Overall, the LIPUS-mediated NMB opening strategy notably enhances nose-to-brain drug delivery efficiency, offering a promising platform for treating brain diseases.