Transient and Efficient Vascular Permeability Window for Adjuvant Drug Delivery Triggered by Microbeam Radiation

Background: Microbeam Radiation Therapy (MRT) induces a transient vascular permeability window, which offers novel drug-delivery system for the preferential accumulation of therapeutic compounds in tumors. MRT is preclinical cancer treatment modality that spatially fractionates synchrotron X-rays into micrometer-wide planar microbeams can induce permeability, especially immature tumor vessels, without compromising perfusion. Here, we characterized this phenomenon using Chicken Chorioallantoic Membrane (CAM) and demonstrated its potential human glioblastoma xenografts mice. Methods: developing CAM was exposed to planar-microbeams 75 Gy peak dose with Synchrotron X-rays. Similarly, mice harboring were microbeam doses 150 Gy, followed by Cisplatin. Tumor progression documented Magnetic Resonance Imaging (MRI) caliper measurements. Results: exhibited beginning 15 min post-irradiation, reaching from 45 2 h, ending 4 h. We have deemed period “permeability window”. Morphological analysis showed partially fragmented endothelial walls as cause increased transport FITC-Dextran surrounding tissue extravasation 100 nm microspheres (representing upper range nanoparticles). In xenografts, MRI measurements combined dramatically reduced size 2.75-fold 5.25-fold, respectively, compared or Cisplatin alone. Conclusions: provides mechanism drug delivery increasing transpermeability while preserving vessel integrity. This window increases index currently available chemotherapeutics could be other agents such Nanoparticles/Antibodies/etc.