Researcher: Demirci, Gözde
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Demirci, Gözde
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Publication Metadata only The effects of histamine receptor antagonists and RhoA inhibitor on histamine-induced blood-brain barrier disruption(Wiley, 2022) Polat, Fidan Şeker; Yılmaz, Canan Uğur; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Department of Chemistry; Akcan, Uğur; Temizyürek, Arzu; Özen, Deniz; Demirci, Gözde; Akbulak, İrem; Üzbe, Ayşe Selin; Üzbe, Pakize Pelin; Acar, Havva Funda Yağcı; Kaya, Mehmet; Ahıshalı, Bülent; PhD Student; Other; Other; Master Student; Master Student; Other; Other; Faculty Member; Faculty Member; Faculty Member; Department of Chemistry; Graduate School of Health Sciences; School of Medicine; N/A; Graduate School of Sciences and Engineering; N/A; N/A; N/A; College of Sciences; School of Medicine; School of Medicine; Koç University Hospital; N/A; 357912; N/A; N/A; N/A; N/A; N/A; 178902; 10486; 9509Publication Metadata only Bypassing pro-survival and resistance mechanisms of autophagy in EGFR-positive lung cancer cells by targeted delivery of 5FU using theranostic Ag2S quantum dots(Royal Soc Chemistry, 2019) Akkoç, Yunus; Gözüaçık, Devrim; N/A; N/A; N/A; N/A; Department of Physics; Department of Chemistry; Demirci, Gözde; Duman, Fatma Demir; Bavili, Nima; Kiraz, Alper; Acar, Havva Funda Yağcı; PhD Student; Master Student; PhD Student; Faculty Member; Faculty Member; Department of Physics; Department of Chemistry; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; School of Medicine; College of Sciences; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; N/A; 22542; 178902Targeted drug delivery systems that combine imaging and therapeutic functions in a single structure have become very popular in nanomedicine. Near-infrared (NIR) emitting Ag2S quantum dots (QDs) are excellent candidates for this task. Here, we have developed PEGylated Ag2S QDs functionalized with Cetuximab (Cet) antibody and loaded with an anticancer drug, 5-fluorouracil (5FU). These theranostic QDs were used for targeted NIR imaging and treatment of lung cancer using low (H1299) and high (A549) Epidermal Growth Factor Receptor (EGFR) overexpressing cell lines. The Cet conjugated QDs effectively and selectively delivered 5FU to A549 cells and provided significantly enhanced cell death associated with apoptosis. Interestingly, while treatment of cells with free 5FU activated autophagy, a cellular mechanism conferring resistance to cell death, these EGFR targeting multimodal QDs significantly overcame drug resistance compared to 5FU treatment alone. The improved therapeutic outcome of 5FU delivered to A549 cells by Cet conjugated Ag2S QDs is suggested as the synergistic outcome of enhanced receptor mediated uptake of nanoparticles, and hence the drug, coupled with suppressed autophagy even in the absence of addition of an autophagy suppressor.Publication Metadata only Alendronate-functionalized poly(amido amine) cryogels of high-toughness for biomedical applications(Elsevier Sci Ltd, 2020) Guven, Melek Naz; Altuncu, Seckin; Gulyuz, Umit; Okay, Oguz; N/A; Department of Chemistry; Demirci, Gözde; Acar, Havva Funda Yağcı; Master Student; Faculty Member; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902Novel bisphosphonic acid-functionalized poly(amido amine) (PAA) macromers were synthesized through aza-Michael addition of sodium alendronate (ALE) and 5-amino-1-pentanol (AP) to N,N'-methylene bisacrylamide at two different molar ratios, with macmmer only having AP as comparison control. The macromers were photopolymerized to cryogels whose swelling, biodegradation and mineralization properties were studied. Biodegradation was most strongly affected by the macromer molecular weight. In mineralization studies, the control cryogel nucleated HAP, the others another type of biological apatite; the extent of mineralization depending on ALE concentration. Cryogel-apatite composites were studied by SEM, FTIR, XRD and thermogravimetric analysis. Mechanical tests reveal compressions up to 97% for cryogels, showing their high toughness. Young's modulus and compressive fracture stress increase with ALE content to 10 kPa and 2.2 +/- 0.4 MPa, respectively. The modulus increased significantly in mineralization due Ca2+-ALE bindings forming physical cross-links. Degradation products of ALE-containing cryogels showed dose, composition and cell type dependent cytotoxicity when incubated with osteosarcoma cells lines, Saos-2 and U-2 OS, and healthy C2C12 muscle cells.Publication Metadata only A leucine aminopeptidase activatable photosensitizer for cancer cell selective photodynamic therapy action(Elsevier Sci Ltd, 2021) N/A; N/A; N/A; Department of Chemistry; N/A; Department of Physics; Department of Chemistry; Department of Chemistry; Arslan, Büşra; Bilici, Kübra; Demirci, Gözde; Almammadov, Toghrul; Khan, Minahil; Sennaroğlu, Alphan; Acar, Havva Funda Yağcı; Kölemen, Safacan; Master Student; PhD Student; Master Student; Researcher; PhD Student; Faculty Member; Faculty Member; Faculty Member; Department of Physics; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Boron and Advanced Materials Application and Research Center (KUBAM) / Koç Üniversitesi Bor ve İleri Malzemeler Uygulama ve Araştırma Merkezi (KUBAM); Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; College of Sciences; N/A; N/A; N/A; N/A; N/A; 23851; 178902; 272051Activity based photosensitizers (PS) continue to attract great attention as they enable selective photodynamic therapy action on cancer cells while sparing normal cells even under light irradiation. Sensitivity to specific enzymes that are differentially overexpressed in cancer cells is crucial in the design of activatable PSs. In this direction, we report here, for the first time, a leucine aminopeptidase (LAP) activatable PDT agent (HCL), which is a red-shifted, water soluble and photostable brominated hemicyanine derivative. HCL was activated by endogenous LAP enzyme selectively in A549 (lung) and HCT116 (colon) cancer cells containing high LAP levels and induced effective photocytotoxicity with negligible dark toxicity. Furthermore, the fluorescence of the parent bromo-hemicyanine core was restored upon LAP-based activation in cancer cells. On the other side, no remarkable phototoxicity or fluorescence turn-on was detected in healthy L929 cells. Thus, HCL serves as an effective and tumour associated LAP-sensitive phototheranostic agent. We believe different cancer-associated analytes can be utilized in combination with near-IR absorbing scaffolds in the scope of activatable PDT designs to enrich the tumour-selective PS arsenal.Publication Metadata only (Bis)phosphonic acid-functionalized poly(ethyleneimine)- poly(amido amine)s for selective in vitro transfection of osteosarcoma cells(Amer Chemical Soc, 2021) Güven, Melek Naz; Altuncu, Seçkin; Konca, Yeliz Utku; Avcı, Duygu; N/A; Department of Chemistry; Demirci, Gözde; Acar, Havva Funda Yağcı; Master Student; Faculty Member; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902Osteosarcoma is aggressive bone cancer, whose treatment has not changed significantly for the past few decades. Although gene therapy methods have emerged as potential treatment routes, the need for efficient and nontoxic gene delivery systems targeting osteosarcoma cells remains a challenge. High-molecular-weight poly(ethyleneimine)s (PEIs) are used as universal transfection agents; however, they cause significant cytotoxicity. on the other hand, poly(amido amine)s (PAAs) are biocompatible, biodegradable polymers with promising transfection efficiency, which should be improved further. In this paper, we combined low-molecular-weight branched PEI (1800 Da) and PAA macromers functionalized with various amounts of (bis)phosphonic acid groups and pentanol (via 5-amino-1-pentanol (AP)). The (bis)phosphonic acid groups on these polymers (PAEIs) are intended to facilitate bone targeting. The molecular weights of the PAEI polymers were between 2600 and 8600 g/mol. Their cytotoxicities and green fluorescence protein (GFP) transfection efficiencies were tested on an osteosarcoma cell line (U-2 OS cells), which is challenging to transfect, and healthy muscle cells (C2C12). Both the cytotoxicity and transfection efficiency of PAEIs were affected by the phosphonic acid (via APA, 2-aminoethyl phosphonic acid) or bisphosphonic acid (via ALE, sodium alendronate) content of the polymers. PAEIs are more cytocompatible than both linear and branched 25 kDa PEI. ALE-containing PAEIs provided better transfection than APA-containing ones. The most efficient PAEI polymer, containing a 0.7:0.3 AP/ALE ratio, displayed a transfection efficiency that was five times higher than that of 25 kDa PEI with dramatically better cytocompatibility. This is comparable to FuGENE, but PAEI is more advantageous in selective transfection of the U-2 OS. This set of polymers may be promising candidates for targeted gene therapy of osteosarcoma.Publication Metadata only Irgacure 2959-functionalized poly(ethyleneimine)s as improved photoinitiators: enhanced water solubility, migration stability and visible-light operation(Royal Soc Chemistry, 2021) Eren, Tugce Nur; Kariksiz, Neslihan; Tuncel, Duygu; Okte, Neren; Avci, Duygu; N/A; Department of Chemistry; Demirci, Gözde; Acar, Havva Funda Yağcı; Master Student; Faculty Member; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902Two novel water soluble polymeric photoinitiators (PPIs) (PEI-I2959 and PEI-I2959-Ts) for free radical polymerization have been synthesized by introducing 2-hydroxy-4 '-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959 or I2959) functionality into branched poly(ethyleneimine) (M-w = 1800 g mol(-1)). These PPIs show an excellent water-solubility of 35-45 g L-1, thus exceeding the solubility of I2959 by 7-9-fold. PPIs show strong absorbance at 274 nm (epsilon similar to 2-3 times larger than that of I2959); and less prominent peaks at 320 and 380 nm for PEI-I2959 and PEI-I2959-Ts, respectively, in water. The aza-Michael addition (similar to 10% conversion) and high photopolymerization efficiencies (90-100% conversion) under both UV and visible light are obtained by photo-differential scanning calorimetry (photo-DSC) and Real-Time Fourier Transform Infrared (RT-FTIR) spectroscopy. The photopolymerization mechanisms involve charge transfer complex formation, verified by absorption studies and enabling visible light polymerization; and a Type I mechanism. PEI-I2959-Ts exhibits 8 times higher migration stability than I2959 due to its high molecular weight. In tests against NIH/3T3 and L929 mouse embryonic fibroblast cells using the MTT cell viability assay, the non-cytotoxicity of PEI-I2959-Ts is shown and PEI-I2959 shows reasonable cell viability at lower concentrations, indicating that PPIs have potential usage in biomaterials.Publication Metadata only Development of near-infrared region luminescent N-acetyl-L-cysteine-coated Ag2S quantum dots with differential therapeutic effect(Future Medicine Ltd, 2019) Erkısa, Merve; Arı, Ferda; Ulukaya, Engin; Department of Chemistry; N/A; N/A; Department of Chemistry; Buz, Pelin; Demirci, Gözde; Duman, Fatma Demir; Acar, Havva Funda Yağcı; Undergraduate Student; PhD Student; Master Student; Faculty Member; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); College of Sciences; Graduate School of Science and Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; N/A; 178902Aim: N-acetyl-L-cysteine (NAC) is a free radical scavenger. We developed NAC-coated Ag2S (NAC-Ag2S) quantum dot (QD) as an optical imaging and therapeutic agent. Materials & methods: QDs were synthesized in water. Their optical imaging potential and toxicity were studied in vitro. Results: NAC-Ag2S QDs have strong emission, that is tunable between 748 and 840 nm, and are stable in biologically relevant media. QDs showed significant differences both in cell internalization and toxicity in vitro. QDs were quite toxic to breast and cervical cancer cells but not to lung derived cells despite the higher uptake. NAC-Ag2S reduces reactive oxygen species (ROS) but causes cell death via DNA damage and apoptosis. Conclusion: NAC-Ag2S QDs are stable and strong signal-generating theranostic agents offering selective therapeutic effects.Publication Metadata only The improved killing of both androgen-dependent and independent prostate cancer cells by etoposide loaded SPIONs coupled with NIR irradiation(Royal Society of Chemistry (RSC), 2022) Erkısa, Merve; Ulukaya, Engin; N/A; N/A; N/A; N/A; Department of Chemistry; Onbaşlı, Kübra; Demirci, Gözde; Muti, Abdullah; Sennaroğlu, Alphan; Acar, Havva Funda Yağcı; Researcher; Master Student; PhD Student; Faculty Member; Faculty Member; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); N/A; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; School of Medicine; College of Sciences; N/A; N/A; N/A; 205925; 178902Etoposide (Eto) is a toxic drug that shows promise in treating prostate cancer (PCa) but confers significant side effects, and has poor solubility and bioavailability. Nanoparticles are quite successful in overcoming such problems. Multifunctional nanoparticles that provide an opportunity to perform combination therapy have attracted great interest in recent years. Superparamagnetic iron oxide nanoparticles (SPIONs) are popular in various biomedical applications, including magnetic resonance imaging, drug delivery, magnetic hyperthermia and recently in photothermal therapy, combining imaging with therapy. Here, for the enhanced killing of PCa cells that are either androgen-dependent or not, the combination of SPION based Eto delivery and mild hyperthermia triggered by laser irradiation is proposed for the first time in the literature. For the encapsulation of Eto, highly stable, small, polyacrylic acid coated SPIONs were conjugated with bovine serum albumin (BSA) (Eto-BSA@PAA@SPION). Eto-BSA@PAA@SPION with 9% drug content produced better chemotherapeutic outcomes than free Eto on both androgen-dependent/castration sensitive LNCaP and androgen-independent/castration-resistant PC3 and DU145 PCa cells by enhancing drug internalization. Single and short irradiation of Eto-BSA@PAA@SPION treated cells at 808 nm improved the drug release and sensitized cells for Eto, hence, increasing the toxicity dramatically in all studied PCa cell lines. Caspase-mediated apoptosis, DNA damage, and ROS generation were detected in the treated cells, increasing with the Eto dose and laser treatment. The IC50 for Eto is reduced to 0.08 mu g mL(-1), 0.13 mu g mL(-1) and 2.8 mu g mL(-1) with laser/Eto-BSA@PAA@SPION for LNCaP, DU145 and PC3 cells, respectively. These are the lowest IC50 values seen in the literature for Eto on these cell lines so far, suggesting that the demonstrated nanoparticles and treatment approaches have great potential to treat various PCa cells at low doses of the drug under mild laser treatment conditions.Publication Metadata only Bisphosphonate-functionalized poly(amido amine) crosslinked 2-hydrox-yethyl methacrylate hydrogel as tissue engineering scaffold(Elsevier, 2021) Güven, Melek Naz; Balaban, Burcu; Okay, Oğuz; Avcı, Duygu; N/A; Department of Chemistry; Demirci, Gözde; Acar, Havva Funda Yağcı; Master Student; Faculty Member; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902The first water soluble, bisphosphonate (BP, not bisphosphonic acid)-functionalized poly(amido amine) macromer (PAA-BP) is synthesized and used as a crosslinker for synthesis of a biodegradable and biocompatible hydrogel for tissue engineering scaffolds. The synthesis of PAA-BP is performed in three steps, the first two giving the control macromers (PAA-NHBoc and PAA-NH2): i) Michael addition reaction of N,N'-methylene bisacrylamide and N-Boc-1,6-hexanediamine (acrylamide/amine ratios of 1.2), ii) deprotection of Boc-protected amine groups, iii) Michael addition reaction of the amine groups with tetraethyl vinylidene bisphosphonate. The degree of BP substitution is 50% and molecular weight of the PAA-BP macromer is found to be 4800 g/mol. These macromers are incorporated into hydrogels by copolymerization with 2-hydroxyethyl methacrylate and the influence of bisphosphonate functionality on hydrogel properties; degradation, swelling, mechanical and mineralization, is investigated. The mineralization abilities, hence the mechanical properties of the hydrogels are strongly influenced by the BP functionality; PAA-BP forming strong (E = 83 +/- 1 kPa) hydrogel-apatite composites, PAA-NH2 also working to a lesser degree (E = 54 +/- 3 kPa). Cytocompatibility of the hydrogels is observed on Saos-2 human osteosarcoma, U-2 OS human bone osteosarcoma epithelial, C2C12 mouse myoblast muscle and NIH mouse embryonic fibroblast 3T3 cells. PAA-BP crosslinked hydrogels facilitate adhesion of C2C12 cells after mineralization. In summary, BP-functionalized hydrogel may have a potential impact on bone tissue engineering.Publication Open Access Cetuximab-Ag2S quantum dots for fluorescence imaging and highly effective combination of ALA-based photodynamic/chemo-therapy of colorectal cancer cells(Royal Society of Chemistry (RSC), 2021) Mohammad Hadi, Layla; Yaghini, Elnaz; Loizidou, Marilena; MacRobert, Alexander J.; Department of Chemistry; N/A; Department of Physics; Acar, Havva Funda Yağcı; Bayır, Ali; Hashemkhani, Mahshid; Demirci, Gözde; Muti, Abdullah; Sennaroğlu, Alphan; Researcher; PhD Student; Master Student; PhD Student; Faculty Member; Department of Chemistry; Department of Physics; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); College of Sciences; Graduate School of Sciences and Engineering; 178902; N/A; N/A; N/A; N/A; 23851Colorectal cancer (CRC) has a poor prognosis and urgently needs better therapeutic approaches. 5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) based photodynamic therapy (PDT) is already used in the clinic for several cancers but not yet well investigated for CRC. Currently, systemic administration of ALA offers a limited degree of tumour selectivity, except for intracranial tumours, limiting its wider use in the clinic. The combination of effective ALA-PDT and chemotherapy may provide a promising alternative approach for CRC treatment. Herein, theranostic Ag2S quantum dots (AS-2MPA) optically trackable in near-infrared (NIR), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) and loaded with ALA for PDT monotherapy or ALA/5-fluorouracil (5FU) for the combination therapy are proposed for enhanced treatment of EGFR(+) CRC. AS-2MPA-Cet exhibited excellent targeting of the high EGFR expressing cells and showed a strong intracellular signal for NIR optical detection in a comparative study performed on SW480, HCT116, and HT29 cells, which exhibit high, medium and low EGFR expression, respectively. Targeting provided enhanced uptake of the ALA loaded nanoparticles by strong EGFR expressing cells and formation of higher levels of PpIX. Cells also differ in their efficiency to convert ALA to PpIX, and SW480 was the best, followed by HT29, while HCT116 was determined as unsuitable for ALA-PDT. The therapeutic efficacy was evaluated in 2D cell cultures and 3D spheroids of SW480 and HT29 cells using AS-2MPA with either electrostatically loaded, hydrazone or amide linked ALA to achieve different levels of pH or enzyme sensitive release. Most effective phototoxicity was observed in SW480 cells using AS-2MPA-ALA-electrostatic-Cet due to enhanced uptake of the particles, fast ALA release and effective ALA-to-PpIX conversion. Targeted delivery reduced the effective ALA concentration significantly which was further reduced with codelivery of 5FU. Delivery of ALA via covalent linkages was also effective for PDT, but required a longer incubation time for the release of ALA in therapeutic doses. Phototoxicity was correlated with high levels of reactive oxygen species (ROS) and apoptotic/necrotic cell death. Hence, both AS-2MPA-ALA-Cet based PDT and AS-2MPA-ALA-Cet-5FU based chemo/PDT combination therapy coupled with strong NIR tracking of the nanoparticles demonstrate an exceptional therapeutic effect on CRC cells and excellent potential for synergistic multistage tumour targeting therapy.