Researcher: Kölemen, Safacan
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Kölemen, Safacan
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Publication Metadata only Selective monitoring and treatment of neuroblastoma cells with hydrogen sulfide activatable phototheranostic agent(Elsevier, 2023) Kepil, Dilay; Elmazoglu, Zubeyir; Ozogul, Naz; Gunbas, Gorkem; N/A; Department of Chemistry; N/A; Department of Chemistry; Dırak, Musa; Almammadov, Toghrul; Çetin, Sultan; Kölemen, Safacan; PhD Student; Researcher; PhD Student; Faculty Member; Department of Chemistry; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; College of Sciences; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; N/A; 272051Activity-based photosensitizers (aPSs) are highly attractive as they offer improved selectivity and better therapeutic outcome in the scope of photodynamic therapy (PDT). Here, a hydrogen sulfide (H2S) responsive iodinated resorufin-based PS (RHS) was developed to treat neuroblastoma cancer cells selectively. RHS was shown to be a phototheranostic agent as it turned on its fluorescence signal and singlet oxygen (O-1(2)) generation capability after reacting with H2S. RHS exhibited remarkable sensitivity towards H2S and proved to be highly cytotoxic in H2S rich SH-SY5Y human neuroblastoma cells upon light irradiation. In contrast, no photocytotoxicity was observed in H2S deficient nonmalignant fibroblast L929 cells. RHS marks the first example of a resorufin-based H2S activatable photo-theranostic agent, which paves the way for effective treatment of neuroblastoma through PDT modality.Publication Metadata only Directing chemiluminescent dioxetanes to mitochondria: a cationic luminophore enables in vitro and in vivo detection of cancer cells upon enzymatic activation(Elsevier B.V., 2023) Department of Chemistry; N/A; N/A; Department of Chemistry; N/A; N/A; N/A; N/A; N/A; Department of Chemistry; Gündüz, Hande; Acari, Alperen; Çetin, Sultan; Almammadov, Toghrul; Değirmenci, Nareg Pınarbaşı; Dırak, Musa; Cingöz, Ahmet; Kılıç, Eda; Önder, Tuğba Bağcı; Kölemen, Safacan; Researcher; Master Student; PhD Student; Researcher; PhD Student; PhD Student; Researcher; Master Student; Faculty Member; Faculty Member; Department of Chemistry; N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; N/A; College of Sciences; Graduate School of Health Sciences; Graduate School of Sciences and Engineering; College of Sciences; Graduate School of Health Sciences; Graduate School of Sciences and Engineering; N/A; Graduate School of Sciences and Engineering; School of Medicine; College of Sciences; 224496; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 184359; 272051A mitochondrion targeted and leucine aminopeptidase (LAP) activatable 1,2-dioxatane based chemiluminescent probe (MCL) for detection of LAP activity in living cancer cells and tumor bearing mice was reported. MCL displayed a selective and sensitive turn-on response in aqueous solutions upon reacting with the LAP enzyme. In cell culture studies, a selective luminescence intensity increase was observed in cancer cell lines, suggesting that MCL can differentiate between cancer and normal cells and allows detection of varying endogenous LAP concentrations. Using fluorescence imaging with a commercial Mitotracker dye, MCL was also shown to localize mitochondria in cancer cell lines. Furthermore, MCL was used to image tumors in mice models. MCL marks not only the first ever example of a mitochondria targeted chemiluminescent probe, but also the first ever example of an organelle targeted 1,2-dioxetane derivative. © 2023 Elsevier B.V.Publication Metadata only A hydrogen peroxide responsive resorufin-based phototheranostic agent for selective treatment of cancer cells(Elsevier Sci Ltd, 2021) Department of Chemistry; Department of Chemistry; Almammadov, Toghrul; Kölemen, Safacan; Researcher; Faculty Member; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Koç University Boron and Advanced Materials Application and Research Center (KUBAM) / Koç Üniversitesi Bor ve İleri Malzemeler Uygulama ve Araştırma Merkezi (KUBAM); College of Sciences; College of Sciences; N/A; 272051Enhanced selectivity towards cancer cells is one of the most essential features sought in new generation photodynamic therapy (PDT) agents in order to minimize the side effects on healthy cells and to improve the efficacy of the treatment. In this direction, one promising approach is to design activatable photosensitizers, which tend to stay in an OFF state and get activated only in cancer cells with tumor-associated stimuli. Based on this idea, herein we introduced a hydrogen peroxide (H2O2) activatable iodinated resorufin (RR-1) as a redshifted, water soluble and cancer cell selective photosensitizer. RR-1 exhibited high singlet oxygen quantum yield in aqueous solutions upon reacting with H2O2 and induced selective photocytotoxicity in colorectal (HCT116) and triple negative breast (MDA MB-231) cancer cells, which contain high level of reactive oxygen species (ROS). Additionally, fluorescence signal of the iodo-resorufin core was restored upon cleavage of the cage unit in these cancer cells. In contrast, very low photocytotoxicity and negligible fluorescence enhancement were observed in normal fibroblast (NIH-3T3) cells. RR-1 not only marks the first example of a H2O2 activatable resorufin-based photosensitizer but also represents the first ever resorufin-based theranostic agent. We anticipate that iodo-resorufin scaffold can be easily modified with different masking units towards realization of highly selective and efficient phototheranostic agents for treatment of various cancer cells.Publication Metadata only An easily available lysosomal-targeted ratiometric fluorescent probe with aggregation induced emission characteristics for hydrogen polysulfide visualization in acute ulcerative colitis(Royal Society of Chemistry (RSC), 2021) Xiang, Chunbai; Li, Chunbin; Xiang, Jingjing; Luo, Yuan; Peng, Jiaofeng; Deng, Guanjun; Wang, Jianguo; Li, Hongchun; Zhang, Pengfei; Gong, Ping; Cai, Lintao; Department of Chemistry; Kölemen, Safacan; Faculty Member; Department of Chemistry; College of Sciences; 272051Hydrogen polysulfide (H2Sn, n >1), as a direct oxidizing form of hydrogen sulfide, is closely associated with intestinal diseases such as ulcerative colitis (UC). A probe that can selectively detect H2Sn in the pathological environment of UC is in urgent demand. Ratiometric probes are powerful in the quantitative detection of H2Sn in living organisms. Herein, we developed a ratiometric fluorescent probe TCFPB-H2Sn for selective detection of H(2)S(n)in vitro and in vivo. Significantly, TCFPB-H2Sn demonstrated a fast, sensitive and specific detection performance for H2Sn, and has excellent lysosomal targeting ability and aggregation-induced emission (AIE) characteristics. More importantly, TCFPB-H2Sn was the first probe to achieve endogenous H2Sn imaging in acute ulcerative colitis successfully.Publication Metadata only A responsive aie-active fluorescent probe for visualization of acetylcholinesterase activity in vitro and in vivo(Royal Soc Chemistry, 2022) Xiang, Chunbai; Dirak, Musa; Luo, Yuan; Peng, Yonglin; Cai, Lintao; Gong, Ping; Zhang, Pengfei; Department of Chemistry; Kölemen, Safacan; Faculty Member; 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); College of Sciences; 272051Acetylcholinesterase (AChE) is a significant enzyme, which plays critical roles in numerous physiological and pathological processes. Thus, selective, and sensitive real-time imaging of AChE activity in vivo has great importance to further understand its contribution to cellular activities and to develop diagnostic tools for several disease states including neurodegenerative disorders and cancer. To this end, we introduced an AChE selective light up fluorescent probe (TCFPB-AChE) with aggregation induced emission (AIE) characteristics to visualize AChE activity both in vitro and in vivo. TCFPB-AChE displayed a selective turn-on fluorescence response upon addition of AChE with a very low detection limit. TCFPB-AChE was further used to image endogenous AChE activity in a glioblastoma cell line and Alzheimer's disease mice brain tissue with a high signal to noise ratio. In addition to these, the probe was also utilized to visualize varying concentrations of AChE in living mice brains in vivo. Remarkably, TCFPB-AChE marks the first ever example of an AChE responsive AIE-based fluorescent probe.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 New class of red absorbing activatable PDT drugs(Amer Chemical Soc, 2019) Atakan, Gizem; Gunaydin, Gurcan; Gunbas, Gorkem; Department of Chemistry; Department of Chemistry; Almammadov, Toghrul; Kölemen, Safacan; Researcher; Faculty Member; Department of Chemistry; College of Sciences; College of Sciences; N/A; 272051N/APublication Metadata only Singlet oxygen probes: diversity in signal generation mechanisms yields a larger color palette(Elsevier Science Sa, 2021) Akkaya, Engin Umut; Department of Chemistry; Department of Chemistry; Gündüz, Hande; Kölemen, Safacan; Researcher; Faculty Member; 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); N/A; College of Sciences; College of Sciences; 224496; 272051The detection and imaging of singlet oxygen produced by natural processes, or by photochemical and chemical reactions has become an important goal in probe design. The short half-life and solvent sensitive nature of the singlet oxygen makes this detection highly challenging. At the same time, since singlet oxygen can be the precursor of other reactive oxygen species (ROS), it is crucial to have a selective probe for singlet oxygen in the presence of other oxidizing species. The challenge is immense, yet there are already brilliant examples of smart probe design. This review mechanistically classifies and discusses what is being done in order to obtain a selective response and at the same time, push the signalling events towards longer wavelengths of the visible spectrum. (C) 2020 Elsevier B.V. All rights reserved.Publication Metadata only Reaction-based bodipy probes for selective bio-imaging(Elsevier Science Sa, 2018) Akkaya, Engin U.; Department of Chemistry; Kölemen, Safacan; Faculty Member; Department of Chemistry; College of Sciences; 272051Complex intracellular environment of cells, which involves interaction of a large variety of bio-molecules, is a dynamic medium with full of important information that can be recovered as well as many unanswered questions. It is highly critical to image and track biologically relevant molecules in their native media without interfering with the regular cellular processes in order to gather as much data as possible to illuminate intricacies of the biological mechanisms. To that end, small-molecule fluorescent probes have been extensively developed during the last few decades with the help of current advances in imaging technologies. Although conventional probes utilizing non-covalent supramolecular interactions with the analyte of interest are successful, significant effort has been also put into the design of reaction-based probes (chemodosimeters). Chemodosimeters exploit selective reactions of analytes with fluorophores in attempt to improve the selectivity of the probes, address the limitations of former sensors and broaden the palette of useful probes. Various types of fluorophore scaffolds can be used in the design of chemodosimeters for visualization of different analytes. In this review, we highlight the 4,4-difluoro-4bora-3a,4a-diaza-s-indacene (BODIPY) based chemodosimeters which have been used to image bio-thiols, reactive oxygen/nitrogen species, and gaseous molecules in living cells.Publication Metadata only Organo-soluble dendritic zinc phthalocyanine: photoluminescence and fluorescence properties(Taylor & Francis Inc) Yabas, Ebru; Bicer, Emre; Baser, Pinar; Kul, Mehmet; Department of Chemistry; Department of Chemistry; Almammadov, Toghrul; Kölemen, Safacan; Researcher; Faculty Member; Department of Chemistry; College of Sciences; College of Sciences; N/A; 272051In this study, the spectroscopic measurements of the second generation dendritic zinc phthalocyanine (phthalocyanine dendrimer with tris) 2 were made and its potential to be used in optoelectronic applications was investigated. To examine the intramolecular energy transfer properties, fluorescence quantum yields were calculated and the contribution of first (phthalocyanine dendrimer with triethyl methanetricarboxylate) 1 and second 2 generation dendrimers to this energy transfer was investigated. The photoluminescence properties and optical band gap of the second generation zinc phthalocyanine 2 were investigated depending on the temperature. In addition, the quantum efficiency of singlet oxygen was calculated to evaluate the usability of this compound in photodynamic therapy. Also, aggregation behavior of compound 2 was examined in different solvents (DMF, DMSO and THF) and different concentrations in THF. To the best of our knowledge, this is the first study to examine the photoluminescence properties and temperature dependent changes of dendritic phthalocyanines.
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