Despite surgical and medical advances, the prognosis for patients with malignant gliomas remains grim. To address this challenge, we propose a program that will combine-for the first time-two major advances in technology for treating diffuse malignant glioma: novel drugs that target glioma stem cells (GSCs) and new nanotechnology-based delivery systems designed for use with convection-enhanced delivery (CED). We believe a biology-based design approach, in which we select drugs that have high activity against the cells that are most important in the persistence of brain tumors, will allow us to design controlled release nanoparticles for CED of drugs that are optimized for the treatment of gliomas. In this project, we will test the hypothesis that drug-loaded, polymer nanoparticles can be delivered to brain tumors by CED, and that loading these nanoparticles with drugs specifically selected for their biological activity against GSCs can enhance treatment of intracranial tumors. We will test this hypothesis by completion of an inter-related set of specific aims: optimization of the properties of nanoparticles for most effective delivery via CED;characterization of novel agents with enhanced activity against GSCs;and controlled delivery of novel agents for treatment of intracranial human gliomas in immunocompromised rats.

Public Health Relevance

Malignant gliomas are the most common primary malignant brain tumors in adults. More than 15,000 new cases are diagnosed in the United States each year. This research project will result in the development of new methods for the treatment of malignant gliomas.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA149128-03
Application #
8444707
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Fu, Yali
Project Start
2011-03-01
Project End
2016-02-29
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
3
Fiscal Year
2013
Total Cost
$290,527
Indirect Cost
$114,982
Name
Yale University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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