Browsing by Subject "Photochemotherapy."

Now showing 1 - 10 of 10

Unknown
Chiral Bodipy dyes & photosensitizers for photodynamic therapy and dye-sensitized solar cells
(2013) Çakmak, Yusuf
Bodipy 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.
Open Access
Covalently functionalized MSNs as potential photosensitizing agents for PDT
(2011) Türkşanlı Kaplan, Merve
Photodynamic 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.
Open Access
Design, synthesis and characterization of activatable photosensitizers for photodynamic therapy
(2012) Çakmak, Fatma Pir
Search 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.
Unknown
Fluorescence detection of biological thiols and axially chiral bodipy derivatives and alternative methodologies for singlet oxygen generation for photodynamic action
(2014) Kölemen, Safacan
Calorimetric 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.
Open Access
Molecular logic gates in the activity modulation of potential PDT agents & rational design of selective chloride sensors
(2013) Erbaş-Çakmak, Sündüs
Considering 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.
Unknown
Near-IR absorbing Bodipy functionalized Spions : a potential magnetic nanoplatform fo diagnosis and therapy
(2012) Ertem, Elif
Photodynamic therapy (PDT), especially with the recent advances in photosensitizer design has already been established as a noninvasive technique for cancer treatment. In PDT, photosensitizers (PSs) are targeted to tumor sites either actively or passively, and are irradiated with a laser of appropriate wavelength. The stimulated PSs transfer excitation energy to endogenous oxygen converting it to reactive oxygen species (ROS) that can kill tumor cells. Up to now, numerous nanomaterials tailored to suitable size, have been studied for effective delivery of PSs. Recently, Near IR-based absorbing nanomaterials which 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. In addition, imaging of these nanomaterials carrying PSs is very important in order to prevent damage to the healthy tissues upon irradiation. Magnetic resonance imaging (MRI) is a powerful technique due to its excellent spatial resolution and depth for in vivo imaging. In this study, a multidisciplinary approach was utilized to create MRI active, near IR-based functional nanomaterials. This approach involves (i) nanochemistry to prepare silica coated super paramagnetic iron oxide (core-shell) nanoparticles, (ii) organic chemistry to synthesize four different type of near- IR absorbing Bodipy derivatives as PSs, and (iii) spectroscopy to verify singlet oxygen production. Four different type of Bodipy based PSs were covalently attached to 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 the use in diagnosis and therapy.
Unknown
Non-covalently functionalized SWNTs as potential delivery agents for novel BODIPY*based PDT sensitizers & the design and synthesis of dendritic light harvesters
(2009) Erbaş, Sündüs
Photodynamic therapy (PDT) is a non-invasive method used for the treatment of a number of diseases including certain cancers and some cardiovascular diseases. Photodynamic action depends on absorbance of photosensitizer (PS) in near IR region of the spectrum and subsequent generation of cytotoxic singlet oxygen in the vicinity of the PS. Carbon nanotubes are widely used for biomedical applications due to their inertness, biocompatibility, cellular internalization, facile and multi-modification. We have synthesized and characterized novel water soluble boradiazaindacene (BODIPY)-based PS, noncovalently attached on to the single wall carbon nanotube (SWNT). We have observed that near infrared absorbing photosensitizer preserve its singlet oxygen generation capability upon adsorption on SWNT. We have demonstrated that SWNTs can be used as the delivery vehicle of PS for the use in PDT. In the second part of this research, multichromatic cascade-type light harvesting BODIPY dendrimers were synthesized and highly efficient energy transfer was observed. Successful channeling of energy in a predefined region of the dendrimer was revealed.
Open Access
Photosensitizers for photodynamic action and synthesis of modules for a molecular demultiplexer
(2014) Durgut, Tuğçe
Photodynamic therapy (PDT) is a new therapeutic methodology that uses light as a distinguishing tool for the treatment of diseased cells. In recent years PDT has become one of the most preferred therapies because it is innocent for the healthy cells and tissues while diagnosing and curing the malignant cells and tissues. Bodipy is one of the most favorite fluorophore in this field due to its excellent chemical and physical properties. Logic gates are widely used in modern technology as the fundamentals of logical operations for the development of science. The progressive advances leads to the emergence and growth of molecular logic gates. Molecular logic gates can be used for the diagnosis and therapies of disease which are originated from the heredity. In addition, they occupy an important place in the theoretical and practical use of photodynamic therapy. In the first part of my thesis, we designed and synthesized a calix[4]arene-Bodipy conjugate molecule as a carrier for the photodynamic therapy agents. It is an amphiphilic delivery molecule that is utilized for the curing of tumor tissues. In the second part, we synthesized modules for molecular logic gate function, DEMUX (demultiplexer), serving as a theranostic device which selects either singlet oxygen channel or energy transfer between the modules depending on the inputs. The superiority of the project is that it serves a realistic pathway for the PDT.
Open Access
Sensing and sensitizer activation by biological thiols and 1,2-dioxetanes based chemiluminescence probes
(2014) Turan, İlke Şimşek
Biologically important biothiols like Cystein (Cys), Homocystein (Hcy) and Glutathione (GSH) are vital for the maintenance of cellular redox status and alterations in their levels is linked to a number of severe diseases such as AIDS, cancer and Alzheimer‟s therefore the design and synthesis of nitroolefin functionalized bodipy dyes responding to biological thiols by both absorbance and emission changes have been accomplished. Through the incorporation of hydrophilic groups, bright signaling of biothiols in the longer wavelength region of the visible spectrum is deemed to operate in biological environment. With this knowledge, bioconjugation of the nitroolefin functionalized dyes with thiol groups like those belonging to cysteine residues on proteins has been proved via large spectral changes and targeted to visualize dynamics of proteins, cell-cell interactions, mechanisms of life cycles of proteins. Hence, the result suggests that nitroolefin functionalization of BODIPY dyes is a promising way to sense biological thiols and hence labeling proteins having thiol groups. Since GSH plays vital roles in the oxidative stress exists within the cells and thus, high concentration of it is the indication of cancer development, design and synthesis of cancer related parameter based activation of bodipy based photosensitizers have been achieved to enhance spatiotemporal selectivity in photonic sensitization of dissolved molecular oxygen and thus, improves the potential and practice of photodynamic therapy and their effectiveness are validated by cell culture studies. Chemiluminescence in principle can provide a rapid, qualitative and/or quantitative test for analytes of interest; because of that synthesis of novel probes for the sensing of biologically important (fluoride) anion have been devised to combine the power of chemiluminescence and self immolative amplifiers which offers a chemical avenue for enhancing the signal produced in response to a given analyte. Through the development of chemiluminogenic perspective for sensing of palladium ions, rapid and selective response of probe to palladium ions with regardless of their charge in aqueous environment have been accomplished. Considering the convenience of the methods and substantial results, we are confident that other probes combining the power of chemiluminescence will emerge.
Open Access
Tetrastyryl-BODIPY dyes as potential photosensitizers for photodynamic theraphy
(2011) Yeşilgül, Nisa
Photodynamic therapy (PDT) is a novel methodology for a wide range of treatments of cancerous and noncancerous diseases. Success of treatment and photodynamic action is highly dependent the performance of PDT agents. Therefore, PDT agents with unique photophysical properties are required in clinical applications. There are several photosensitizers in literature and some are available. However, most of them less than ideal due to limitations such as low molar absorptivity and photo stabilities. In this study, we synthesized near-IR tetrastyryl-Bodipy derivatives as photosensitizers. These sensitizers have strong absorption in therapeutic region and are good photo-generator of singlet oxygen. They are promising for photodynamic therapy with their favorable properties.