Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Review Citation - WoS: 6Citation - Scopus: 8Molecular Trojan Horses for Treating Lysosomal Storage Diseases(Academic Press, 2023) Leal, Andres Felipe; Rintz, Estera; Çelik, Betül; Ago, Yasuhiko; León, Daniel; İnci, Orhan Kerim; Seyrantepe, VolkanLysosomal storage diseases (LSDs) are caused by monogenic mutations in genes encoding for proteins related to the lysosomal function. Lysosome plays critical roles in molecule degradation and cell signaling through interplay with many other cell organelles, such as mitochondria, endoplasmic reticulum, and peroxisomes. Even though several strategies (i.e., protein replacement and gene therapy) have been attempted for LSDs with promising results, there are still some challenges when hard-to-treat tissues such as bone (i.e., cartilages, ligaments, meniscus, etc.), the central nervous system (mostly neurons), and the eye (i.e., cornea, retina) are affected. Consistently, searching for novel strategies to reach those tissues remains a priority. Molecular Trojan Horses have been well-recognized as a potential alternative in several pathological scenarios for drug delivery, including LSDs. Even though molecular Trojan Horses refer to genetically engineered proteins to overcome the blood-brain barrier, such strategy can be extended to strategies able to transport and deliver drugs to specific tissues or cells using cell-penetrating peptides, monoclonal antibodies, vesicles, extracellular vesicles, and patient-derived cells. Only some of those platforms have been attempted in LSDs. In this paper, we review the most recent efforts to develop molecular Trojan Horses and discuss how this strategy could be implemented to enhance the current efficacy of strategies such as protein replacement and gene therapy in the context of LSDs. © 2023Article Citation - WoS: 17Citation - Scopus: 22Protein Corona Formation on Silver Nanoparticles Under Different Conditions(Elsevier, 2022) Tomak, Aysel; Yılancıoğlu, Buket; Winkler, David; Öksel Karakuş, CeydaThe surfaces of nanoparticles become covered by biomolecules in biological fluids. This protein ‘corona’ modifies materials’ characteristics and biological activity. The composition of the protein corona is dynamic, abundant biomolecules that bind first are subsequently replaced by less abundant but more tightly bound ones. Here, we explore the formation of the silver nanoparticle protein corona on exposure to cell culture media containing 10 % fetal bovine serum supplemented Dulbecco's Modified Eagle's medium. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry analysis were used to monitor how different parameters such as incubation time, heating duration, cell culture medium, incubation temperature, and the number of washes affect the nanoparticle–protein corona complex. silver nanoparticles with and without bound proteins were characterized by electron microscopy, dynamic light scattering, and ultraviolet-visible-near-IR spectroscopy. The tetrazolium-based MTT assay was used to determine viability of A549 human lung adenocarcinoma cells treated with silver nanoparticles. Characterization of the nanoparticles before and after protein binding provided insights into their changing morphology on corona formation. Our results confirmed that the physiological environment directly affects protein corona formation on nanoparticle surfaces. In particular, incubation condition-dependent differences in the amount of bound proteins were observed. This work highlights the importance of environmental drivers of protein adsorption, which should be considered when predicting and/or controlling protein targets of silver nanoparticles.Article Citation - WoS: 25Citation - Scopus: 23Synthesis and Characterization of Aicar and Dox Conjugated Multifunctional Nanoparticles as a Platform for Synergistic Inhibition of Cancer Cell Growth(American Chemical Society, 2016) Dağlıoğlu, Cenk; Okutucu, BurcuThe success of cancer treatment depends on the response to chemotherapeutic agents. However, malignancies often acquire resistance to drugs if they are used frequently. Combination therapy involving both a chemotherapeutic agent and molecularly targeted therapy may have the ability to retain and enhance therapeutic efficacy. Here, we addressed this issue by examining the efficacy of a novel therapeutic strategy that combines AICAR and DOX within a multifunctional platform. In this context, we reported the bottom-up synthesis of Fe3O4@SiO2(FITC)-FA/AICAR/DOX multifunctional nanoparticles aiming to neutralize survivin (BIRC5) to potentiate the efficacy of DOX against chemoresistance. The structure of nanoparticles was characterized by dynamic light scattering (DLS), zeta-potential measurement, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and electron microscopy (SEM and STEM with EDX) techniques. Cellular uptake and cytotoxicity experiments demonstrated preferentially targeted delivery of nanoparticles and an efficient reduction of cancer cell viability in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat, and MIA PaCa-2). These results indicate that the multifunctional nanoparticle system possesses high inhibitory drug association and sustained cytotoxic effect with good biocompatibility. This novel approach which combines AICAR and DOX within a single platform might be promising as an antitumor treatment for cancer.