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)
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Gene and Drug Delivery Systems Study Section (GDD)
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Tucker, Jessica
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Johns Hopkins University
Biomedical Engineering
Schools of Medicine
United States
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Wang, Ting; Gilkes, Daniele M; Takano, Naoharu et al. (2014) Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis. Proc Natl Acad Sci U S A 111:E3234-42
Sunshine, Joel C; Perica, Karlo; Schneck, Jonathan P et al. (2014) Particle shape dependence of CD8+ T cell activation by artificial antigen presenting cells. Biomaterials 35:269-77
Kim, Jayoung; Sunshine, Joel C; Green, Jordan J (2014) Differential polymer structure tunes mechanism of cellular uptake and transfection routes of poly(*-amino ester) polyplexes in human breast cancer cells. Bioconjug Chem 25:43-51
Guerrero-Cázares, Hugo; Tzeng, Stephany Y; Young, Noah P et al. (2014) Biodegradable polymeric nanoparticles show high efficacy and specificity at DNA delivery to human glioblastoma in vitro and in vivo. ACS Nano 8:5141-53
Bishop, Corey J; Kim, Jayoung; Green, Jordan J (2014) Biomolecule delivery to engineer the cellular microenvironment for regenerative medicine. Ann Biomed Eng 42:1557-72
Bishop, Corey J; Kim, Jayoung; Kozielski, Kristen L et al. (2014) Highlights from the latest articles in nanomedicine. Nanomedicine (Lond) 9:945-7
Tzeng, Stephany Y; Green, Jordan J (2013) Therapeutic nanomedicine for brain cancer. Ther Deliv 4:687-704
Sunshine, Joel C; Green, Jordan J (2013) Nanoengineering approaches to the design of artificial antigen-presenting cells. Nanomedicine (Lond) 8:1173-89
Li, Cuicui; Tzeng, Stephany Y; Tellier, Liane E et al. (2013) (3-aminopropyl)-4-methylpiperazine end-capped poly(1,4-butanediol diacrylate-co-4-amino-1-butanol)-based multilayer films for gene delivery. ACS Appl Mater Interfaces 5:5947-53
Kozielski, Kristen L; Tzeng, Stephany Y; Green, Jordan J (2013) Bioengineered nanoparticles for siRNA delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol 5:449-68

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