Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 13Citation - Scopus: 14Synthesis of Albumin Nanoparticles in a Water-Miscible Ionic Liquid System, and Their Applications for Chlorambucil Delivery To Cancer Cells(Elsevier, 2022) Akdoğan, Yaşar; Sözer, Sümeyra Çiğdem; Sözer, Sümeyra Çiğdem; Başol, Merve; Akdoğan, Yaşar; Çakan Akdoğan, Gülçin; 03.09. Department of Materials Science and Engineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringSerum albumin has been a preferred protein to generate biodegradable and non-toxic nanoparticles (NPs) for drug delivery applications. Different methods applied for the preparation of serum albumin NPs mostly used organic solvents. Here, we prepared serum albumin NPs in an ionic liquid (IL) system. ILs are considered to be green and designer solvents with unique properties that can replace organic solvents in the synthesis of albumin NPs. Bovine serum albumin (BSA) proteins dissolved in water were transformed into BSA NPs in a water/ Triton™X (TX-100), 1-butanol/1-butyl-3-methylimidazolium trifluoromethanesulfonate (BmimCF3SO3) microemulsion-like system by using a high-speed homogenizer and crosslinker glutaraldehyde. The obtained BSA NPs have been used in drug loading and release studies with a hydrophobic anticancer drug chlorambucil (Chl). Drug loading increased as increasing the ratio of Chl incubated with BSA NPs. Monitoring the drug release by UV–Vis spectroscopy revealed a burst release at first 4 h, but two-thirds of drugs stayed with NPs upon diffusion method. On the other hand, cellular uptake of Chl loaded BSA NPs caused a significant MCF7 breast cancer cell death, whereas free Chl and unloaded BSA NPs did not have a significant effect on the cell viability. Furthermore, in vivo toxicity assessment of BSA NPs obtained in the IL system was conducted in the zebrafish animal model. It showed that zebrafish body is able to eliminate BSA NPs without any toxic side effects and encapsulation of Chl into NPs reduced the toxicity of free Chl. In summary, we showed that BSA NPs with size smaller than 200 nm could be prepared in BmimCF3SO3 mediated system. They can be used for Chl loading (up to 6.9 wt%) with a sustainable release and they induce significant cell death in Chl sensitive cancer cells up to 45% in 24 h. These results indicate that BSA NPs could be prepared alternatively in IL systems and used in drug delivery studies.Article Citation - WoS: 10Citation - Scopus: 10An in Vivo Zebrafish Model Reveals Circulating Tumor Cell Targeting Capacity of Serum Albumin Nanoparticles(Elsevier, 2022) Çakan Akdoğan, Gülçin; Sözer, Sümeyra Çiğdem; Sözer, Sümeyra Çiğdem; Gelinci, Emine; 01. Izmir Institute of TechnologyNanoparticles are promising tools of drug delivery in modern medicine. There is a need for fast and reliable models for in vivo validation of newly developed nanocarriers. Here, we report a fast and easy zebrafish larval model to study the biodistribution and cancer cell targeting capacity of serum albumin nanoparticles in vivo. Fluorescently tagged Bovine Serum Albumin Nanoparticles (BSA-NPs) delivered intravenously to the zebrafish larvae, can be used to study the biodistribution via live imaging. We showed that the BSA-NPs were instantly distributed to the larval vasculature including the brain, without causing any toxicity. The clearance of nanoparticles from the body occurred within few days, which gives sufficient time to study anti-cancer efficiency of the BSA-NPs. Next, we asked whether the BSA-NPs can target the cancer cells in circulation. We established a circulating tumor cell (CTC) xenograft model and described a quantitative method for colocalization and cancer cell death analysis in the intact live organism. We showed that BSA-NPs effectively found and localized to MCF7 cells in vasculature which were killed upon doxorubicin delivery. Interestingly, folic acid coating of BSA-NPs caused faster colocalization but did not increase the overall cell death. This is the first report of the biodistribution, toxicity and anti-cancer effectiveness of serum albumin-based nanoparticles in the zebrafish model. Moreover, here we report for the first time that BSA-NPs are able to target the CTCs in an in vivo model. The zebrafish CTC model and the analysis protocol reported here can be used to assess CTC targeting capacity of nanoparticles and devise patient specific CTC targeting tests.Article Citation - WoS: 5Citation - Scopus: 4Characterization of Water Solubility and Binding of Spin Labeled Drugs in the Presence of Albumin Nanoparticles and Proteins by Electron Paramagnetic Resonance Spectroscopy(Wiley-Blackwell, 2022) Sözer, Sümeyra Çiğdem; Akdoğan, Yaşar; Akdoğan, Yaşar; Sözer, Sümeyra Çiğdem; 03.09. Department of Materials Science and Engineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringElectron paramagnetic resonance (EPR) spectroscopy is an advantageous technique to monitor solubility of drugs in an aqueous solution. In the presence of a drug carrier, the bound and unbound drug fractions can be determined in the same sample simultaneously. To enhance the solubility of hydrophobic drugs, a transporter protein of bovine serum albumin (BSA) can be used directly or in the form of nanoparticle. Moreover, a cationic BSA can be used to enhance anionic drug loading. Here, drugs with different water solubility, salicylic acid (high), ibuprofen (low) and chlorambucil (none) were spin labeled and studied with EPR spectroscopy. Remarkably, it has been shown that albumin nanoparticles are much more effective than albumin proteins in dissolving hydrophobic drugs in water. Furthermore, different drug loading methods were compared, and different from other techniques drug release can be monitored directly from the NPs pellet dissolution by EPR spectroscopy.Article Citation - WoS: 18Citation - Scopus: 20A Simple Desolvation Method for Production of Cationic Albumin Nanoparticles With Improved Drug Loading and Cell Uptake(Editions de Sante, 2020) Sözer, Sümeyra Çiğdem; Akdoğan, Yaşar; Başol, Merve; Çakan Akdoğan, Gülçin; Sözer, Sümeyra Çiğdem; 03.09. Department of Materials Science and Engineering; 01. Izmir Institute of Technology; 03. Faculty of EngineeringThe transport protein albumin has been used as a drug nanocarrier for a long time due to its versatility. Albumin is negatively charged at physiological conditions limiting its anionic drug loading capacity. However, loading of anionic drugs in the albumin nanoparticles (NPs), can be facilitated by albumin cationization. Here, we postulate a simple desolvation method for preparation of cationic albumin NPs with improved anionic drug loading. First, bovine serum albumin was cationized with ethylenediamine. Next, salicylic acid (SA) was added to the cationic bovine serum albumin (cBSA) solution prior to the desolvation. Among different desolvating agents tested, acetonitrile allowed the highest nanoparticle formation yield. The SEM analyses showed that the average size of cBSA NPs decreased from ~200 nm to ~100 nm upon SA loading. Moreover, the drug loading capacity of cBSA NPs was found to increase ~2 fold, and drug release was slower compared to BSA NPs. Finally, a significant increase in cellular uptake of cBSA NPs compared to that of native BSA NPs showed the potential for improved drug delivery. © 2020 Elsevier B.V.