Browsing by Author "Gunduz, Nuray"
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Item Open Access Intracellular accumulation of gold nanoparticles leads to inhibition of macropinocytosis to reduce the endoplasmic reticulum stress(Nature Publishing Group, 2017) Gunduz, Nuray; Ceylan, H.; Güler, Mustafa O.; Tekinay, Ayse B.Understanding the toxicity of nanomaterials remains largely limited to acute cellular response, i.e., short-Term in vitro cell-death based assays, and analyses of tissue-and organ-level accumulation and clearance patterns in animal models, which have produced very little information about how these materials (from the toxicity point of view) interact with the complex intracellular machinery. In particular, understanding the mechanism of toxicity caused by the gradual accumulation of nanomaterials due to prolonged exposure times is essential yet still continue to be a largely unexplored territory. Herein, we show intracellular accumulation and the associated toxicity of gold nanoparticles (AuNPs) for over two-months in the cultured vascular endothelial cells. We observed that steady exposure of AuNPs at low (non-lethal) dose leads to rapid intracellular accumulation without causing any detectable cell death while resulting in elevated endoplasmic reticulum (ER) stress. Above a certain intracellular AuNP threshold, inhibition of macropinocytosis mechanism ceases further nanoparticle uptake. Interestingly, the intracellular depletion of nanoparticles is irreversible. Once reaching the maximum achievable intracellular dose, a steady depletion is observed, while no cell death is observed at any stage of this overall process. This depletion is important for reducing the ER stress. To our knowledge, this is the first report suggesting active regulation of nanoparticle uptake by cells and the impact of long-Term exposure to nanoparticles in vitro. © 2017The Author(s).Item Open Access A modular antigen presenting peptide/oligonucleotide nanostructure platform for inducing potent immune response(Wiley - VCH Verlag GmbH & Co. KGaA, 2017-05) Tohumeken, Sehmus; Gunduz, Nuray; Demircan, M. Burak; Gunay, Gokhan; Topal, Ahmet E.; Khalily, M. Aref; Tekinay, T.; Dana, Aykutlu; Güler, Mustafa O.; Tekinay, Ayse B.The design and development of vaccines, which can induce cellular immunity, particularly CD8+ T cells hold great importance since these cells play crucial roles against cancers and viral infections. Covalent conjugation of antigen and adjuvant molecules has been used for successful promotion of immunogenicity in subunit vaccines; however, the stimulation of the CD8+ T‐cell responses by this approach has so far been limited. This study demonstrates a modular system based on noncovalent attachment of biotinylated antigen to a hybrid nanofiber system consisting of biotinylated self‐assembling peptide and CpG oligodeoxynucleotides (ODN) molecules, via biotin–streptavidin interaction. These peptide/oligonucleotide hybrid nanosystems are capable of bypassing prior limitations related with inactivated or live‐attenuated virus vaccines and achieve exceptionally high CD8+ T‐cell responses. The nanostructures are found to trigger strong IgG response and effectively modulate cross‐presentation of their antigen “cargo” through close proximity between the antigen and peptide/ODN adjuvant system. In addition, the biotinylated peptide nanofiber system is able to enhance antigen uptake and induce the maturation of antigen‐presenting cells. Due to its versatility, biocompatibility, and biodegradability with a broad variety of streptavidin‐linked antigens, the nanosystem shown here can be utilized as an efficient strategy for new vaccine development.