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|Title:||Radiation-Induced Targeted Nanoparticle-Based Gene Delivery for Brain Tumor Therapy||Authors:||Erel-Akbaba, Gulsah
Carvalho, Litia A.
Obeid, Pierre J.
|Affiliations:||Department of Chemistry||Keywords:||Glioblastoma
Solid lipid nanoparticle
|Issue Date:||2019||Part of:||ACS nano||Volume:||13||Issue:||4||Start page:||4028||End page:||4040||Abstract:||
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.
|Appears in Collections:||Department of Chemistry|
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