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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Fu, Yali
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
Engineering (All Types)
Schools of Engineering
New Haven
United States
Zip Code
Chi, David Lei; Song, Eric; Gaudin, Alice et al. (2017) Improved threshold selection for the determination of volume of distribution of nanoparticles administered by convection-enhanced delivery. Comput Med Imaging Graph 62:34-40
Seo, Young-Eun; Bu, Tom; Saltzman, W Mark (2017) Nanomaterials for convection-enhanced delivery of agents to treat brain tumors. Curr Opin Biomed Eng 4:1-12
Song, Eric; Gaudin, Alice; King, Amanda R et al. (2017) Surface chemistry governs cellular tropism of nanoparticles in the brain. Nat Commun 8:15322
King, Amanda R; Corso, Christopher D; Chen, Evan M et al. (2017) Local DNA Repair Inhibition for Sustained Radiosensitization of High-Grade Gliomas. Mol Cancer Ther 16:1456-1469
Saucier-Sawyer, Jennifer K; Seo, Young-Eun; Gaudin, Alice et al. (2016) Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors. J Control Release 232:103-12
Gaudin, Alice; Song, Eric; King, Amanda R et al. (2016) PEGylated squalenoyl-gemcitabine nanoparticles for the treatment of glioblastoma. Biomaterials 105:136-44
Deng, Yang; Yang, Fan; Cocco, Emiliano et al. (2016) Improved i.p. drug delivery with bioadhesive nanoparticles. Proc Natl Acad Sci U S A 113:11453-11458
Adams, Brian D; Wali, Vikram B; Cheng, Christopher J et al. (2016) miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer. Cancer Res 76:927-39
Zhang, Junwei; Cui, Jiajia; Deng, Yang et al. (2016) Multifunctional Poly(amine-co-ester-co-ortho ester) for Efficient and Safe Gene Delivery. ACS Biomater Sci Eng 2:2080-2089
Adams, Brian D; Anastasiadou, Eleni; Esteller, Manel et al. (2015) The Inescapable Influence of Noncoding RNAs in Cancer. Cancer Res 75:5206-10

Showing the most recent 10 out of 26 publications