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: 15Citation - Scopus: 13Environmentally Responsive Dual-Targeting Nanoparticles: Improving Drug Accumulation in Cancer Cells as a Way of Preventing Anticancer Drug Efflux(John Wiley and Sons Inc., 2018) Dağlıoğlu, CenkDrug targeting and stimuli-responsive drug release are 2 active areas of cancer research and hold tremendous potential in the management of cancer drug resistance. In this study, I addressed this issue and focused on the synthesis and characterization of pH-responsive Fe3O4@SiO2(FITC)-BTN/folic acid/DOX multifunctional nanoparticles aiming to increase drug accumulation in malignancies with both dual active targeting and endosomal drug release properties. Dye-doped silica magnetic-fluorescent composite was constructed by a simple coprecipitation of Fe+2/Fe+3 salts followed by sol-gel formation and dual-targeting function was obtained by conjugating folate and biotin moieties on the silica surface of nanoparticles via an esterification reaction. Doxorubicin was then successfully attached on the amine-functionalized nanoparticles using a pH-sensitive Schiff-base formation. The physicochemical characterization of the structure was performed by dynamic light scattering, zeta potential measurement, X-ray diffraction, Fourier transform infrared spectroscopy, electron microscopy techniques, and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated an enhanced intracellular delivery and reduction of cancer cell viability in the cervical carcinoma HeLa cell line. Furthermore, proapoptotic studies showed that the nanoparticles increased the apoptotic rates within the same cancer cells. The preliminary cell tests confirm the potential of these multifunctional nanoparticles against the development of drug resistance in cancer cells.