Adenosine 5'-triphosphate-sensitive potassium channel-mediated blood-brain tumor barrier permeability increase in a rat brain tumor model.

摘要: Brain tumor microvessels/capillaries limit drug delivery to tumors by forming a blood-brain barrier (BTB). The BTB overexpresses ATP-sensitive potassium (K(ATP)) channels that are barely detectable in normal brain capillaries, and which were targeted for permeability modulation. In rat model, we infused minoxidil sulfate (MS), selective K(ATP) channel activator, obtain sustained, enhanced, delivery, including various sized molecules, across the tumors. Glibenclamide, inhibitor, significantly attenuated MS-induced increase. Immunocytochemistry glibenclamide binding studies showed increased density distribution on cells capillary endothelium, was confirmed potentiometric assay endothelial cocultured with cells. MS infusion rats transport vesicle facilitated of macromolecules, Her-2 antibody, adenoviral-green fluorescent protein, carboplatin, tumors, carboplatin increasing survival tumor-bearing rats. channel-mediated increase also demonstrated human, xenograft model. We conclude potential target biochemical modulation antineoplastic selectively