Yazar "Tannous, Bakhos A." seçeneğine göre listele

Listeleniyor 1 - 2 / 2
  • Küçük Resim Yok
    Öğe
    Rabies virus-mimicking liposomes for targeted gene therapy in Alzheimer's disease
    (Elsevier, 2024) Erel Akbaba, Gulsah; Akbaba, Hasan; Karaman, Ozan; Tian, Tian; Tannous, Bakhos A.; Turunc, Ezgi
    RNA interference (RNAi) harbors significant potential for treating neurological disorders; nevertheless, limited efficacy has been discerned. The presence of barriers within the central nervous system, coupled with the inherent instability of nucleic acids within biological conditions, poses formidable challenges in advancing effective gene delivery strategies. In this study, we designed and prepared a virus-mimic non-viral gene vector, rabies virus glycoprotein (RVG29)-decorated liposome (f(Lipo)-RVG29), to deliver small interfering RNAs to the brain. Alzheimer's disease (AD) was chosen as a model of neurodegenerative disease in this context, and b-site APP cleaving enzyme silencing siRNA (siBACE1) was used. The developed liposomal delivery system has a particle size of under 80 nm with a spherical shape, positive zeta potential, and the ability to protect siRNA against nucleases. In vitro studies demonstrate that functionalizing the cationic liposome by the RVG29 targeting ligand significantly enhances the effectiveness of gene delivery and silencing. Examination through ex vivo imaging illustrates an increased deposition of fluorescent-labeled f(Lipo)-RVG29 within brain tissue after 12 h post application. Additionally, the in vivo delivery of f(Lipo)-RVG29 carrying siRNA has substantially suppressed BACE1 expression at both mRNA and protein levels within the brain tissue. Our results suggest that the developed non-viral vector could be a promising gene carrier system combining the synergistic effect of virus-mimic RVG29 ligand with bioinspired liposome that imitates the natural lipid bilayers of cell membranes for braintargeted RNAi therapeutics.
  • Küçük Resim Yok
    Öğe
    Radiation-Induced Targeted Nanoparticle-Based Gene Delivery for Brain Tumor Therapy
    (Amer Chemical Soc, 2019) Erel-Akbaba, Gulsah; Carvalho, Litia A.; Tian, Tian; Zinter, Max; Akbaba, Hasan; Obeid, Pierre J.; Chiocca, E. Antonio; Weissleder, Ralph; Kantarci, Ayse Gulten; Tannous, Bakhos A.
    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.