Imaging and Treatment of Gliomas Using Nanoparticles

DESCRIPTION (provided by applicant): The long term goal of the proposed project is to develop a novel nanoparticle for both molecular imaging and treatment of brain tumors. This Phase I project will contribute to this goal by the synthesis and characterization of a polyacrylamide based-nanoparticle which can be manufactured to contain a contrast agent (Gadolinium). The primary goals of the present proposal are to investigate approaches for enhancement of the efficiency of cellular internalization of the Gadolinium containing nanoparticles into tumor cells so that the efficacy of gadolinium neutron capture therapy (GNCT) can be optimized. We hypothesize that delivery of these nanoparticles with gadolinium contrast agent will provide an opportunity to use MRI to detect the presence and spatial extent of the uptake in tumor tissue. In addition, delivery of gadolinium to tumor tissue intracellularly will provide an opportunity for treatment using GNCT. The purpose of this Phase I application is to provide data revealing that this nanoparticle can be synthesized and internalized in cells, rendering them sensitive to GNCT. We propose to demonstrate that attachment of RGD containing peptides or Avidin to Gd-containing nanoparticles results in enhanced binding and internalization. This proposal will provide proof-of-principle relating to the synthesis, function (imaging) and therapeutic efficacy. It is anticipated that the results obtained from the proposed studies will provide the foundation for future development of these novel nano-structure-based strategies for non-invasive in vivo imaging of tumors and delivery of therapeutic payloads.