Browsing by Subject "Photodynamic therapy"
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Item Open Access Activatable photosensitizers: agents for selective photodynamic therapy(Wiley-VCH Verlag, 2017) Li, X.; Kolemen, S.; Yoon, J.; Akkaya, E. U.Recent developments in the design of bifunctional and activatable photosensitizers rejuvenate the aging field of photodynamic sensitization and photodynamic therapy. While systematic studies have uncovered new dyes that can serve as potential photosensitizers, the most promising results have come from studies aimed at gaining precise control over the location and rate of cytotoxic singlet oxygen generation. As a consequence, higher selectivities and efficiencies in photodynamic treatment protocols are now within reach. This feature article highlights the variety of approaches that have been pursued to improve photodynamic therapy and to transform simple photosensitizers into smarter theranostic agents.Item Open Access A bifunctional photosensitizer for enhanced fractional photodynamic therapy: singlet oxygen generation in the presence and absence of light(Wiley-VCH Verlag, 2016) Turan, I. S.; Yildiz, D.; Turksoy, A.; Gunaydin, G.; Akkaya, E. U.The photosensitized generation of singlet oxygen within tumor tissues during photodynamic therapy (PDT) is self-limiting, as the already low oxygen concentrations within tumors is further diminished during the process. In certain applications, to minimize photoinduced hypoxia the light is introduced intermittently (fractional PDT) to allow time for the replenishment of cellular oxygen. This condition extends the time required for effective therapy. Herein, we demonstrated that a photosensitizer with an additional 2-pyridone module for trapping singlet oxygen would be useful in fractional PDT. Thus, in the light cycle, the endoperoxide of 2-pyridone is generated along with singlet oxygen. In the dark cycle, the endoperoxide undergoes thermal cycloreversion to produce singlet oxygen, regenerating the 2-pyridone module. As a result, the photodynamic process can continue in the dark as well as in the light cycles. Cell-culture studies validated this working principle in vitro.Item Open Access Chiral Bodipy dyes & photosensitizers for photodynamic therapy and dye-sensitized solar cells(Bilkent University, 2013) Çakmak, YusufBodipy is a molecule with many superior properties. After its discovery in 1968, most of the features were not recognized until mid 1990s. Thereafter, many research papers and patents have been produced and the number of publications and citations is still on the rise today. An important fraction of the research done with this fluorophore is in chemosensing field to probe various analytes including anions, cations and even biomolecules. However, in this research we have focused on different areas of subjects and tried to find novel applications for these dyes. First, we designed orthogonal bodipy dimers for efficient triplet photosensitization without heavy atoms in contrast to most other sensitizers and efficient singlet oxygen generation was achieved (Φ∆=0.51). In the second project, calix[4]arene molecules were designed and synthesized as carriers for photodynamic therapy, potentially behaving as a molecular basket carrying the agents to the tumor tissues. Later, we focused on obtaining axial chiral molecules by using solely bodipy dyes, and we were able to obtain enantiopure fragments were separated by using chiral HPLC. These rare molecules are desirable for modern biological labeling and advanced optoelectronic devices. Finally, we designed bodipy dyes for dye sensitized solar cells by adapting relevant functional groups, and following synthesis work, we constructed cells to assess the design parameters via measuring the electrical output results.Item Open Access Controlled singlet oxygen generation via plasmonic heating of gold nanorods(Bilkent University, 2015-08) Karataş, TuğçePhotodynamic therapy (PDT) is the up-and-coming and developing methodology in order to treat various cancer tissues. The success of therapeutic action is directly related to the presence of cytotoxic singlet oxygen (SO) in tumor tissues. However, the feasibility of PDT is bounded by two major factors, hypoxia and the requirement of incident light penetration through cancer tissue. With these considerations, we have combined aromatic endoperoxides and gold nanorods so as to accomplish the possible restrictions. In this project, we synthesized and characterized both PEGylated anthracenic endoperoxides and gold nanorods separately and then further characterization was achieved for the combination of gold nanorods and aromatic endoperoxides. We have successfully proved that the thermal decomposition of endoperoxide molecule was carried out by irradiation of gold nanorods that resulted in the generation of both singlet and molecular oxygen.Item Open Access Covalently functionalized MSNs as potential photosensitizing agents for PDT(Bilkent University, 2011) Türkşanlı Kaplan, MervePhotodynamic therapy (PDT) is a novel approach for the treatment of some cancers and other non-malignant diseases. PDT aims to kill cancer tissue by the generation of singlet oxygen as a result of excitation of the photosensitizer (PS) by illuminating with a light source at a certain wavelength. Mesoporous silica nanoparticles are promising in PDT issue due to their chemical inertness, biocompatibility, lowtoxicity, hydrophility and ease of surface modification. We have synthesized and characterized novel boradiazaindacene (BODIPY)-based PS that is covalently attached to the pore of mesoporous silica nanoparticles (MSNs). We have observed that near infrared absorbing photosensitizer attached MSNs successfully generate cytotoxic singlet oxygen.Item Open Access Cytotoxicity of multifunctional surfactant containing capped mesoporous silica nanoparticles(Royal Society of Chemistry, 2016) Yildirim, A.; Turkaydin, M.; Garipcan, B.; Bayındır, MehmetThis paper reports the synthesis of silica capped surfactant (cetyltrimethylammonium bromide; CTAB) and dye (Rose Bengal; RB) containing mesoporous silica nanoparticles (MSNs). Capping the pores of the surfactant containing MSNs with a thin silica layer decreased the immediate surfactant originated cytotoxicity of these particles without affecting their long term (3 days) cytotoxicity. Also, the silica capping process almost completely prevented the hemolytic activity of the surfactant containing MSNs. In addition, improved uptake of silica capped MSNs compared to the uncapped particles by cancer cells was demonstrated. The delayed cytotoxicity, low hemolytic activity, and better cellular uptake of the silica capped MSNs make them promising for the development of safe (i.e. with fewer side effects) yet efficient theranostic agents. These nanocarriers may release the loaded cytotoxic molecules (CTAB) mostly after being accumulated in the tumor site and cause so minimal damage to the normal tissues and blood components. In addition, the nanoscale confinement of RB molecules inside the pores of MSNs makes the particles brightly fluorescent. Furthermore, it was demonstrated that due to the singlet oxygen generation capability of the RB dye the silica capped MSNs can be also used for photodynamic therapy of cancer. © 2016 The Royal Society of Chemistry.Item Open Access Design, synthesis and characterization of activatable photosensitizers for photodynamic therapy(Bilkent University, 2012) Çakmak, Fatma PirSearch for new noninvasive methods for diseases has been significant question for years. Therapeutic properties of light are combined with proper chromophore in order to create fundamentals of photodynamic therapy which is a new treatment modality for cancer and other various non-oncological diseases. The method relies on the activation of photosensitizer by using light of certain wavelength and generation of cytotoxic singlet oxygen species in response. Reactive oxygen species kill the targeted tissue within smaller effective diameter through apoptosis/ necrosis mechanism. Through this method, new PDT agents can be proposed and their properties can be tuned by manipulation of other photophysical processes. In this thesis, synthesis, characterization novel water soluble, near IR absorbing Bodipy photosensitizer will be discussed. As opposed to other photosensitizers in literature, this photosensitizer is rationally designed to have singlet oxygen generation capability only in cancer tissue as a result of glutathione triggered activation.Item Open Access Design, synthesis and characterization of orthogonal bodipy trimers and progress tpwards a singlet oxygen probe(Bilkent University, 2015-08) Bila, Jose LuisSeveral methods of fighting cancer have been proposed over the years after it was discovered. Photodynamic therapy (PDT) has been part of these methods for many years therefore; too much financial effort has been spent on this field. Since PDT relays on three important components namely: Sensitizer, molecular oxygen and light, our group has worked and published several photosensitizers derived from BODIPY over the years. In this thesis two different ideas to be used in PDT are introduced. First, Heavy atom free orthogonal BODIPY trimmers are introduced for the first time in literature and they are believed to work according to DS-TR principle. Effective singlet oxygen productions were obtained up to 0.53 quantum yields. The second topic is the use of BODIPY and 1,3-DiphenylIsobenzofuran hybrids as a singlet oxygen sensor. This sensor is meant to work based on PeT and ICT mechanisms. No further experimental methods were applied to this molecule after synthesis however; we intend to use it for in-vivo singlet oxygen experiments in the future.Item Open Access Designing excited states: theory-guided access to efficient photosensitizers for photodynamic action(2011) Cakmak, Y.; Kolemen, S.; Duman, S.; Dede, Y.; Dolen, Y.; Kilic, B.; Kostereli, Z.; Yildirim, L. T.; Dogan, A. L.; Guc, D.; Akkaya, E. U.The in silico design of tetraradical S 1 states was validated experimentally through synthesis, followed by characterization including phosphorescence measurements, use of trap molecules, and cell culture studies, leading to a series of orthogonal dimers of Bodipy chromophores with remarkable singlet oxygen efficiencies (see picture). A new path for the rational development of efficient photosensitizers is thus revealed.Item Open Access Energy transfer, photosensitization and sensing with novel bodipy compounds and their supramolecular assemblies(Bilkent University, 2017-06) Yeşilgül, NisaFluorescent dyes have been used for decades in many applications due to their versatility, sensitivity and many other useful properties. Since their discovery in 1968, BODIPY dyes have come forward and have been used in many fields of research such as photodynamic therapy, anion/cation sensing, dye-sensitized solar cells. In this thesis, novel applications of fluorescent dyes, mainly based on BODIPY fluorophores are reported. In the first project, a photosensitizer derived from erythrosine attached to a luminol derivative is presented. The main purpose was to achieve photosensitization without requiring external excitation with light. In another project, we synthesized and characterized a series of heavy atom substituted BODIPY based photosensitizers. In a related study, the photophysical properties of a BODIPY based chemosensor substituted with benzo-21-crown-7 units were studied in the presence of various -diamino alkanes. Then, we designed a BODIPY based probe sensitive to bioreductive conditions known to be prevalent in hypoxic cancer cells. In the final chapter, we present a mechanically interlocked energy transfer cassette consisted of a distyryl-BODIPY acceptor and two donor units.Item Open Access An exploration of new avenues regarding deep tissue penetration and higher singlet oxygen efficiencies: novel near-IR photosensitizers for photodynamic therapy(TÜBİTAK, 2019) Yeşilgül, Nisa; Kılıç, BilalA series of novel BODIPY-bearing electron-withdrawing groups at the meso position are reported here. According to the optical measurements, it may be clearly seen that the introduction of electron-donating groups into 3,5-positions and the presence of electron-withdrawing groups at the meso position of the BODIPY core resulted in spectacular bathochromic shifts (up to ~ 304 nm), and the projected photosensitizers had absorption bands in the therapeutic window of the electromagnetic spectrum (600–900 nm). The absorption maxima of compounds 4, 5, 6, and 7 were at 886 nm, 890 nm, 760 nm, and 761 nm, respectively. The singlet oxygen generation experiments revealed that compounds 6 and 7, with high singlet oxygen quantum yields (0.52 and 0.93, respectively), were excellent and promising candidates for photodynamic therapy. The singlet oxygen quantum yield of 0.93 was the highest reported value so far for BODIPY-based photosensitizers.Item Open Access Fluorescence detection of biological thiols and axially chiral bodipy derivatives and alternative methodologies for singlet oxygen generation for photodynamic action(Bilkent University, 2014) Kölemen, SafacanCalorimetric and luminescent detection of biological thiols namely cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) have attracted great interest due to the their biological significance. There are many reported fluorescent probes for Cys and Hcy, however selective probe designs for GSH remained elusive. We represented in thesis (Chapter 3) a BODIPY based selective fluorescent probe for the in vitro detection of GSH in cancer cell lines. Photodynamic therapy (PDT) is one of the promising and developing treatment modality for certain indications. Therapeutic action is achieved by the generation of cytotoxic singlet oxygen (SO). Most critical compartment of SO production pathway is the sensitizer molecule. In order to get effective inter-system crossing, which is highly needed for singlet oxygen generation, common strategy is to incorporate heavy atoms on sensitizers. However, presence of heavy atoms increases the dark toxicity that is not desired in clinical applications. In Chapter 4, we are introducing a new concept for activatable heavy atom free sensitization of PDT by designing novel orthogonal BODIPY derivatives and detailed computational analysis of this new concept. While dealing with orthogonal BODIPYs, we synthesized for the first time two axially chiral BODIPY derivatives and characterized the enantiopure products, which holds great promise for enantioselective sensing applications (Chapter 5). PDT has two major problems, which are light penetration depth of the incident light and the hypoxia. These two restrictions are addressed in chapter 6, by combining gold nanorods and aromatic endoperoxides.Item Open Access Generation, storage and delivery of singlet oxygen by a multifunctional agent(Bilkent University, 2017-04) Türksoy, AbdurrahmanPhotodynamic therapy (PDT) relies on thephoto sensitized generation of sin- glet oxygen (by consuming dissolved oxygen) within tumortissues whose oxygen level is already low enough to make this treatment self-limiting. In certain ap- plications, hypoxia induced by photosensitizer is minimized by introducing light intermittently (fractionalPDT) in order to allow time for the replenishment of cellular oxygen, resulting in more effective treatment. In this particular study, we demonstrated that a photosensitizer with an attached 2-pyridone module to halogenated di-styryl BODIPY would be useful in fractional PDT. Upon illumi- nation of photosensitizer (PYR) with a light at specific wavelength in therapeutic window the endoperoxide of 2-pyridone isgenerated along with singlet oxygen. During the time required for replenishment of cellular oxygen the endoperoxide undergoes cycloreversion to produce singlet oxygen, regenerating the2-pyridonemoiety. Such mechanism enables continuation of photodynamic process in the dark, resulting improved fractional photodynamic thearpy drug validated by cell culture studies in vitro.Item Open Access Glycosylated conjugated oligomer and chlorophyll based nanoparticles for photodynamic therapy(Bilkent University, 2023-01) Oduncu, EzgiNanomaterial-based therapeutic agents are drawing a lot of attention because numerous capabilities, including drugs, targeting groups, and photoactive units, can be combined on one platform to treat infectious diseases and cancer. In this regard, two different nanomaterials and their nanomedicine applications were re-ported. Firstly, red-emitting glycosylated conjugated oligomer (COL) nanopar-ticle was prepared and hybrid conjugation with gold nanoparticles was prepared by the nanoprecipitation method in order to examine photothermal applications. Due to their authentic electronic and optical characteristics, showing high sin-glet oxygen production ability, enabling control of the sizes of nanoparticles by acetyl groups in the side chains, enhancing their stability, and improving cell permeability via the hydrophobic effect they are promoting photosensitizers for photodynamic therapy. Secondly, chlorophyll, a natural photo absorbent, was ex-tracted from spinach leaves, and chlorophyll nanoparticles were prepared by nano-precipitation method because of their promoting properties which are high bio-compatibility, low production cost, and natural reductive chemical atmosphere, containing plenty of hydrogen atoms and being environmentally friendly. Then, hybrid conjugation with gold nanoparticles was prepared to investigate photother-mal therapy application. Both of the nanoparticles showed a high generation ability of reactive oxygen species (ROS) even at low light intensities and short exposure times which makes nanoparticles an ideal photosensitizer. From the antibacterial experiment, when Gram-negative (Escherichia coli, E. coli) bacteria were incubated with chlorophyll-based nanoparticles, a reduction up to 2.8-log and 2.33-log in colony-forming units (CFUs) was obtained under light irradiation for Chl-Au and Chl nanoparticles, respectively. Also, these nanoparticles showed minimal dark cytotoxicity (0.32-log and 0.15-log). On the other hand, conjugated oligomer-based nanoparticles precipitated in bacterial suspension and were un-able to pass across the cell wall of bacteria which was proved by SEM images and 4 mm and 5 mm inhibition zone were recorded for COL and COL-Au nanopar-ticles which are highly lower than ampicillin (7 mm). Along with these results, it is deduced that conjugated oligomer nanoparticles are not proper for antibac-terial photodynamic applications although the interaction between the bacterial cell wall and nanoparticle was promoted with gold conjugation. For anticancer photodynamic therapy applications, MCF-7 breast cancer cells were treated with these nanoparticles in the dark and under white light illumination for 20 min-utes, and the decline in cell viability was recorded at 50 %, 60 %, and 58 %, 72 %reduction for Chl, Chl-Au, and COL, Chl-Au nanoparticles, respectively. Also, they demonstrated dark cytotoxicity with the increment of concentration. Ad-ditionally, they also demonstrated the capacity for cellular imaging due to their inherent fluorescent properties, which might be used for image-guided PDT ap-plications. Along with this, the cytotoxicity results were supported by displaying the cellular uptake of nanoparticles and their surrounding the nucleus of breast cancer cells.Item Open Access Imaging of intracellular singlet oxygen with bright BODIPY dyes(Elsevier Ltd, 2021-04) Kaya, S.; Kwon, N.; Kim, G.; Bila, Jose Luis; İsmaiel, Yahya A.; Yoon, J.; Seven, Özlem; Akkaya, E.Singlet oxygen is a cytotoxic reactive species which is involved in the photodynamic therapy of cancer. It is also known to be produced endogenously in most eukaryotic cells and implicated in many biochemical processes, including apoptotic response. We now report that Bodipy based fluorescent dyes with singlet oxygen reactive modules, signal the intracellular generation of singlet oxygen through photosensitization. We believe long wavelength probes of singlet oxygen, based on this approach will be highly valuable.Item Open Access Molecular logic gates in the activity modulation of potential PDT agents & rational design of selective chloride sensors(Bilkent University, 2013) Erbaş-Çakmak, SündüsConsidering the time arrow of science, things are getting smaller and smarter as the information grows immensely. More is known about the molecular and genetic basis of diseases, and therapies become more personalized accordingly. In parallel, organic devices are becoming progressively intelligent. Molecular logic gates increase the flexibility in functionality of the Boolean logic operations, and allow the creation of demanding complex functionalities for different purposes. The missing link between the design of any kind of complex logic operation and assignment of a real function is addressed by our work. A dual-activatable photosensitizer acting as an AND logic gate enables a more selective photodynamic therapy with the use of biologically relavant concentrations of acid and glutathione. Additionally, with a combinatorial therapy and imaging approach, a proof of principle theranostic device with DEMUX logic behaviour is developed to select between singlet oxygen generation and emission in response to an address input (acid) in organic solvent. In another project, relay of information between two independent logic gates embedded into a physically constraining microenvironment was successfully demonstrated to report the activity of a pH-activatable photosensitizer as an enhanced emission. Independently, a series of highly selective fluorescent chloride anion sensors based on BODIPY-triazolophane conjugate are introduced with a surprisingly large dynamic response range.Item Open Access Nanostructured materials for biological imaging and chemical sensing(Bilkent University, 2014-11) Yıldırım, AdemIn the recent years, the design and synthesis of fluorescent nanoparticles for biological and chemical sensing applications have received considerable attention due to the excellent photostability and emission intensity of fluorescent nanoparticles and the intrinsic sensitivity of fluorescence based methods. Although considerable progress has been made in their synthesis, there is still need for low-cost and high throughput methods for their widespread utilization in biological and chemical sensing applications. In addition, studies regarding their biocompatibility are necessary to identify the toxicological potential of these nanomaterials. In this context, this thesis seeks new methods for multifunctional fluorescent nanoparticle synthesis and investigates their interactions with living organisms. In addition, it reports the applications of the fluorescent nanomaterials in biological imaging, therapy and chemical sensing applications. First, we report a self-assembly method to prepare PEGylated or peptide functionalized mesoporous silica nanoparticles (MSNs) for cell labeling and drug delivery applications. The good cyto- and blood- compatibility of the functionalized nanoparticles were demonstrated. Next, we demonstrated a surfactant assisted method to synthesize ultrabright silica nanoparticles and studied their in vitro v cytocompatibility with several cell lines. We demonstrated the applications of ultrabright particles in cell labeling, chemo and photodynamic therapy and trace explosive sensing. Then, we discuss a template-free method (porosity difference based selective dissolution strategy) to prepare self-luminescent mesoporous hollow silica nanoparticles with tailored shapes. In addition, we studied the surface effects on blood compatibility of nanoparticles in detail using the MSNs possessing different surface functional groups (ionic, polar, neutral, and hydrophobic). Finally, we investigated the optical properties of polydopamine nanoparticles and showed that fluorescence of asprepared polydopamine nanoparticles can be used for sensitive and selective detection of the dopamine neurotransmitter.Item Open Access Near IR absorbing bodipy-functionalized SPIONs: a potential magnetic nanoplatform for diagnosis and therapy(De Gruyter, 2014) Ertem, E.; Bekdemir, A.; Atilgan, A.; Akkaya, E. U.Photodynamic therapy (PDT), especially with the recent advances in photosensitizer (PS) design, has already been established as a noninvasive technique for cancer treatment. Recently, near-IR-based absorbing PSs that have a rising potency to implement light-triggered tumor ablation have attracted much attention since near-IR light in the 650-850 nm range penetrates more deeply in tissues. Up to now, numerous nanomaterials tailored to suitable sizes have been studied for effective delivery of PSs. In this study, four different types of Bodipy-based PSs were covalently attached to magnetic resonance imaging (MRI) active, biocompatible, and nontoxic nanocarriers and generation of singlet oxygen capabilities were evaluated. It was demonstrated that these core-shell nanoparticles are promising delivery vehicles of PSs for use in diagnosis and therapy.Item Open Access Near-IR absorbing BODIPY derivatives as glutathione-activated photosensitizers for selective photodynamic action(Wiley-VCH Verlag, 2014) Turan, I. S.; Cakmak, F. P.; Yildirim, D. C.; Cetin Atalay, R.; Akkaya, E. U.Enhanced spatiotemporal selectivity in photonic sensitization of dissolved molecular oxygen is an important target for improving the potential and the practical applications of photodynamic therapy. Considering the high intracellular glutathione concentrations within cancer cells, a series of BODIPY-based sensitizers that can generate cytotoxic singlet oxygen only after glutathione-mediated cleavage of the electron-sink module were designed and synthesized. Cell culture studies not only validate our design, but also suggest an additional role for the relatively hydrophobic quencher module in the internalization of the photosensitizer.Item Open Access Non-covalent functionalized SWNTs as delivery agents for novel Bodipy-based potential PDT sensitizers(2009) Erbas, S.; Gorgulu, A.; Kocakusakogullari, M.; Akkaya, E. U.Pyrenyl-functionalized distyryl-Bodipy sensitizer attached non-covalently to SWNTs was shown to generate singlet oxygen when excited at 660 nm with a red LED array; this work emphasizes the potential of SWNT as a viable alternative carrier of bioactive agents, including photodynamic therapy sensitizers. © 2009 The Royal Society of Chemistry.