MRI Monitoring of Cerebral Blood Flow after the Delivery of Nanocombretastatin across the Blood Brain Tumor Barrier

Introduction of polymeric nanoparticles in cancer therapeutics is widely investigated since nanomedicine often enables the intratumoral delivery of drugs with increased efficacy with minimal side effects. In this study MRI monitoring was employed to study the therapeutic effect of nanocombretastatin (G3-CA4) in an orthotopic glioma model. Water insoluble combretastatin (CA4) was conjugated to a small-sized water soluble G3-succinamic acid PAMAM dendrimer. Nanoconstruct sizes were determined by TEM to be 3 to 5 nm. Intravenous (i.v.) delivery of G3-CA4 in an orthotopic glioma model produced a long-lived ischemia accompanied by necrosis at the core of the tumor but leaving a rim of viable tissue. In contrast, delivery of CA4 alone has no therapeutic effect in an experimental rat model of glioma.