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)
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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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Guo, Qiongyu; Bishop, Corey J; Meyer, Randall A et al. (2018) Entanglement-Based Thermoplastic Shape Memory Polymeric Particles with Photothermal Actuation for Biomedical Applications. ACS Appl Mater Interfaces 10:13333-13341
Kim, Jayoung; Shamul, James G; Shah, Sagar R et al. (2018) Verteporfin-Loaded Poly(ethylene glycol)-Poly(beta-amino ester)-Poly(ethylene glycol) Triblock Micelles for Cancer Therapy. Biomacromolecules 19:3361-3370
Lopez-Bertoni, Hernando; Kozielski, Kristen L; Rui, Yuan et al. (2018) Bioreducible Polymeric Nanoparticles Containing Multiplexed Cancer Stem Cell Regulating miRNAs Inhibit Glioblastoma Growth and Prolong Survival. Nano Lett 18:4086-4094
Wilson, David R; Sen, Rupashree; Sunshine, Joel C et al. (2018) Biodegradable STING agonist nanoparticles for enhanced cancer immunotherapy. Nanomedicine 14:237-246
Meyer, Randall A; Mathew, Mohit P; Ben-Akiva, Elana et al. (2018) Anisotropic biodegradable lipid coated particles for spatially dynamic protein presentation. Acta Biomater 72:228-238
Zamboni, Camila G; Kozielski, Kristen L; Vaughan, Hannah J et al. (2017) Polymeric nanoparticles as cancer-specific DNA delivery vectors to human hepatocellular carcinoma. J Control Release 263:18-28
Wilson, David R; Routkevitch, Denis; Rui, Yuan et al. (2017) A Triple-Fluorophore-Labeled Nucleic Acid pH Nanosensor to Investigate Non-viral Gene Delivery. Mol Ther 25:1697-1709
Wilson, David R; Mosenia, Arman; Suprenant, Mark P et al. (2017) Continuous microfluidic assembly of biodegradable poly(beta-amino ester)/DNA nanoparticles for enhanced gene delivery. J Biomed Mater Res A 105:1813-1825
Kim, Jayoung; Mirando, Adam C; Popel, Aleksander S et al. (2017) Gene delivery nanoparticles to modulate angiogenesis. Adv Drug Deliv Rev 119:20-43
Fontaine, Arjun K; Gibson, Emily A; Caldwell, John H et al. (2017) Optical Read-out of Neural Activity in Mammalian Peripheral Axons: Calcium Signaling at Nodes of Ranvier. Sci Rep 7:4744

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