Small molecule systemic chemotherapy has been relatively ineffective in the treatment of malignant solid tumors.This is primarily due to sub-therapeutic drug accumulation within individual brain tumor cells following drug extravasation across the porous blood-brain tumor barrier of malignant solid tumor microvasculature.Nanoparticles of sizes ranging between 7 nm and 10 nm in diameter can be used to deliver therapeutically effective concentrations of small molecule chemotherapy drugs across the blood-tumor barrier into individual tumor cells,since these particles are sufficiently smaller than the 12 nm physiologic upper limit of pore size within the blood-tumor barrier,and maintain peak steady-state blood concentrations for several hours.We have validated the initial therapeutic efficacy of a prototypical imageable nanoparticle bearing chemotherapy,the Gd-G5-doxorubicin dendrimer,in the orthotopic RG-2 rodent malignant glioma model.Here I will present this novel strategy,and discuss the therapeutic implications thereof,in the context of a review of the historical strategies.