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Title: Radiation-Induced Targeted Nanoparticle-Based Gene Delivery for Brain Tumor Therapy
Authors: Erel-Akbaba, Gulsah
Carvalho, Litia A.
Tian, Tian
Obeid, Pierre J. 
Affiliations: Department of Chemistry 
Keywords: Glioblastoma
Targeted therapy
Solid lipid nanoparticle
Issue Date: 2019
Part of: ACS nano
Volume: 13
Issue: 4
Start page: 4028
End page: 4040
Targeted therapy against the programmed cell death ligand-1 (PD-L1) blockade holds considerable promise for the treatment of different tumor types; however, little effect has been observed against gliomas thus far. Effective glioma therapy requires a delivery vehicle that can reach tumor cells in the central nervous system, with limited systemic side effect. In this study, we developed a cyclic peptide iRGD (CCRGDKGPDC)-conjugated solid lipid nanoparticle (SLN) to deliver small interfering RNAs (siRNAs) against both epidermal growth factor receptor (EGFR) and PD-L1 for combined targeted and immunotherapy against glioblastoma, the most aggressive type of brain tumors. Building on recent studies showing that radiation therapy alters tumors for enhanced nanotherapeutic delivery in tumor-associated macrophage-dependent fashion, we showed that low-dose radiation primes targeted SLN uptake into the brain tumor region, leading to enhanced downregulation of PD-L1 and EGFR. Bioluminescence imaging revealed that radiation therapy followed by systemic administration of targeted SLN leads to a significant decrease in glioblastoma growth and prolonged mouse survival. This study combines radiation therapy to prime the tumor for nanoparticle uptake along with the targeting effect of iRGD-conjugated nanoparticles to yield a straightforward but effective approach for combined EGFR inhibition and immunotherapy against glioblastomas, which can be extended to other aggressive tumor types.
Type: Journal Article
Appears in Collections:Department of Chemistry

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