Focused Ultrasound Enhances Brain Delivery of Sorafenib Nanoparticles

Glioblastoma (GBM) is a universally lethal form of brain cancer. The success novel treatments hindered by the blood–brain barrier (BBB), which prevents most drugs from penetrating GBM tumors. Sorafenib (SFB), proapoptotic multikinase inhibitor, has been investigated for treatment GBM; however, survival benefit among patients not improved. Recently, an indocyanine-stabilized nanoparticulate SFB (SFB NPs) with improved tumor accumulation was developed in comparison to alone. Herein, NPs and focused ultrasound (FUS)-mediated BBB disruption assessed enable noninvasive, safe, reversible permeation enhanced accumulation. Treatment FUS yields lower IC50 values (2.7 29 μm 2D 3D U87 cell models vs 7.5 37.1 alone). microbubbles improve uptake cells compared alone (46% increase; p = 0.0123). In vivo, enhances 2.5-fold contralateral hemisphere, 3.6-fold unsonicated brains. conclusion, are promising agent its therapeutic capacity can be potentially when combined FUS-mediated disruption.