Radiation-Induced Targeted Nanoparticle-Based Gene Delivery for Brain Tumor Therapy
Makaleler > Tam Makale · 2019
Yazarlar: Gulsah Erel-Akbaba, Litia A. Carvalho, Tian Tian, Max Zinter, Hasan AKBABA, Pierre J. Obeid, E. Antonio Chiocca, Ralph Weissleder, Ayşe Gülten KANTARCI, Bakhos A. Tannous
ACS Nano, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2019, cilt 13, ss 4028-4040
Özet
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.