Brain cancer, and in particular Glioblastoma (GB), is a deadly disease that is in critical need of new therapies. We propose to develop biodegradable polymeric gene delivery nanoparticles to treat patients with brain cancer. Based on our recent research on evaluating a library of polymeric nanoparticles for gene delivery, ten lead structures will be synthesized and utilized to non-virally and safely deliver DNA to human Glioblastoma Multiforme (GB) cancer cells. Structure-activity relationships for ten closely related biomaterial analogs and the nanoparticles that they form will be probed in vitro in normal human astrocytes and neurospheres as well human intraoperatively obtained GB cells and GB tumor neurospheres. We hypothesize that through biomaterial and nanoparticle selection, nanoparticles can be targeted to brain cancer cells and cancer stem cells over healthy cells. A nanoparticle system will be created and evaluated in vitro and in vivo to non-virally delivery a gene that induces apoptosis in human brain cancer cells, is benign to healthy human cells, and acts in a paracrine fashion. The non-viral particles enter cells and degrade safely, releasing DNA as therapeutics that causes cancer cell death.
In Aim 1, nanoparticles will be synthesized and characterized and cell assays developed.
In Aim 2, mechanisms of action, cell targeting specificity, and efficacy of the nanoparticles will be evaluated in vitro.
In Aim 3, the top three nanoparticle formulations will be evaluated in vivo in an orthotopic human GB mouse model. The long-term aim of this work is to create a new orthogonal clinical approach to treat Glioblastoma.

Public Health Relevance

This research aims to create new nanbiotechnology to treat Glioblastoma, a common and incurable type of brain cancer. This flexible nanoparticle-mediated gene delivery approach may also be applicable to the treatment of other cancers as well.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Tucker, Jessica
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Biomedical Engineering
Schools of Medicine
United States
Zip Code
Mangraviti, Antonella; Tzeng, Stephany Y; Gullotti, David et al. (2016) Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival. Biomaterials 100:53-66
Meyer, Randall A; Green, Jordan J (2016) Shaping the future of nanomedicine: anisotropy in polymeric nanoparticle design. Wiley Interdiscip Rev Nanomed Nanobiotechnol 8:191-207
Bishop, Corey J; Majewski, Rebecca L; Guiriba, Toni-Rose M et al. (2016) Quantification of cellular and nuclear uptake rates of polymeric gene delivery nanoparticles and DNA plasmids via flow cytometry. Acta Biomater 37:120-30
Kozielski, Kristen L; Green, Jordan J (2016) Bioreducible Poly(Beta-Amino Ester)s for Intracellular Delivery of SiRNA. Methods Mol Biol 1364:79-87
Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan et al. (2016) Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain. Biomaterials 84:157-66
Hung, Ben P; Hutton, Daphne L; Kozielski, Kristen L et al. (2015) Platelet-Derived Growth Factor BB Enhances Osteogenesis of Adipose-Derived But Not Bone Marrow-Derived Mesenchymal Stromal/Stem Cells. Stem Cells 33:2773-84
Meyer, Randall A; Sunshine, Joel C; Perica, Karlo et al. (2015) Biodegradable nanoellipsoidal artificial antigen presenting cells for antigen specific T-cell activation. Small 11:1519-25
Bishop, Corey J; Tzeng, Stephany Y; Green, Jordan J (2015) Degradable polymer-coated gold nanoparticles for co-delivery of DNA and siRNA. Acta Biomater 11:393-403
Meyer, Randall A; Green, Jordan J (2015) Biodegradable polymer iron oxide nanocomposites: the future of biocompatible magnetism. Nanomedicine (Lond) 10:3421-5
Bishop, Corey J; Liu, Allen L; Lee, David S et al. (2015) Layer-by-Layer Inorganic/Polymeric Nanoparticles for Kinetically Controlled Multi-gene Delivery. J Biomed Mater Res A :

Showing the most recent 10 out of 30 publications