Browsing by Author "Demirbolat, Gulen Melike"

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PEG4000 modified liposomes enhance the solubility of quercetin and improve the liposome functionality: in vitro characterization and the cellular efficacy
(Scientific and Technological Research Council Turkey, 2022-01-01) Demirbolat, Gulen Melike; Erdogan, Omer; Coskun, Goknil Pelin; Cevik, Ozge
Quercetin, a multifunctional therapeutic agent, is used in various types of cancer. However, its therapeutic effect is limited by virtue of poorly aqueous solubility and instability in the physiological medium. To overcome these limitations, we aimed (i) to design quercetin loaded Liposomes with unlinked-PEG4000 with regard to not only surface modification but also solubility enhancement, and (ii) to investigate the antineoplastic effects on HeLa cells. PEG4000 increased the quercetin solubility 2.2 fold. PEG4000 modified Liposomes displayed small particle size (254 +/- 69 nm), low polydispersity index (0.236 +/- 0.018), favorable zeta potential (-35.4 +/- 0.6 mV), high quercetin encapsulation efficiency (87.6 +/- 5.6\%), and drug loading (22.2 +/- 6.9\%). The homogeneity and particle size of stable PEGylated liposomes were proved by transmission electron microscopy. The drug release was reached up to 65.1 +/- 3.8\% in 6 h. The IC50 value of quercetin loaded PEGylated liposomes was 16.3 mu g/mL on HeLa cells, while that of quercetin was 88.3 mu g/mL. PEGylated liposomes remarkably hampered the adherence and colony formation ability of cells according to crystal violet staining tests. The convenience of PEGylated liposomes for the parenteral application was stated by the hemolysis assay. The high-throughput screening assays based on AO/PI staining proved the drastic decrease of viable cell count. Moreover, qPCR tests based on gene expression levels revealed that the quercetin loaded PEGylated liposomes treatment could be more effective than free quercetin on the mitochondrial apoptosis of lieLa cells. These promising results allow considering further in vivo studies for efficient cancer treatment with quercetin loaded PEG4000 modified liposomes.
Treatment of glioblastoma by photodynamic therapy with the aid of synthesized silver nanoparticles by green chemistry from Citrus aurantium
(MARMARA UNIV, 2021-01-01) Erdogan, Omer; Abbak, Muruvvet; Demirbolat, Gulen Melike; Aksel, Mehran; Pasa, Salih; Donmez Yalcin, Gizem; Cevik, Ozge
Blood brain barrier is very important to provide treatment locally for the treatment of glioblastoma. The use of nanoparticles has shown promise for glioblastoma treatments in recent years. In this study, the effect of the combined treatment of silver nanoparticles (AgNPs) synthesized from Citrus aurantium with photodynamic therapy (PDT) was investigated on U87 glioblastoma cells. AgNPs were characterized by FTIR, zeta potential and SEM images. U87 cells were treated with AgNPs (10 mu g/mL) and/or PDT (0.5 mJ/cm(2)) at 24 h. Cells antiproliferative effect, migration levels, colony formation capability, Bax and Bcl-2 protein/gene expression, and caspase-3 activity levels as apoptotic markers were measured. AgNPs size were found at 141 +/- 3 nm and 18.1 +/- 1.3 mV as zeta potential. It was found that cell proliferation, migration and Bcl-2 protein/gene levels decreased, and Bax protein/ gene levels and caspase-3 activity increased via AgNPs and PDT combined treatment. As a result, nanoparticles synthesized from Citrus aurantium are eco-friendly and their size can cross the blood brain barrier. If AgNPs is used with PDT, it may be a new therapy for clinically treatment of glioblastoma in the future.
Wharton jelly-derived mesenchymal stem cell exosomes induce apoptosis and suppress EMT signaling in cervical cancer cells as an effective drug carrier system of paclitaxel
(PUBLIC LIBRARY SCIENCE, 2022-01-01) Abas, Burcin Irem; Demirbolat, Gulen Melike; Cevik, Ozge
Mesenchymal stem cells can be obtained and multiplied from various sources and have a very high capacity to release exosomes. Exosomes are nano-sized extracellular vesicles containing biological signaling molecules. This study aimed to determine the effect of MSC-derived exosomes as a drug delivery system for paclitaxel in cervical cancer cells. In this study, human MSC were isolated from wharton jelly of umbilical cord tissue (WJ-MSC), and cells were characterized by CD44, CD90, CD105, and CD34 staining. Exosomes were released in WJ-MSC cells with serum-starved conditions for 48 hours, and particle sizes and structures were examined with zeta-sizer and TEM. In addition, exosomes CD9, CD63, and CD81 markers were checked by western blot. Paclitaxel was loaded into exosomes (Exo-PAC) by electroporation and then incubated with Hela cervical cancer cells for 24 hours. TGF-beta, SMAD, Snail, Slug, beta-catenin, Notch, Caspase-3, Caspase-9, Bax, Bcl-2 protein and gene expression levels were analyzed in Hela cells. As a result, low concentration Exo-PAC induced apoptosis, and suppressed epithelial-mesenchymal transition proteins in Hela cells. In this study, it has been demonstrated that WJ-MSCs can be used as drug delivery systems for cervical cancer if exosomes are produced scalably in the future.