Browsing by Subject "Photosensitizer"

Now showing 1 - 9 of 9

Open Access
Chemical modulation of singlet oxygen generation rates in thermal endoperoxide decomposition & novel fluorescent sensors for hyperphosporylated tau proteins
(2016-05) Kaya, Cansu
Chemical control over singlet oxygen generation is an open to improvement because of the importance of this reactive species in biological systems. In the first project, we aimed to synthesize a silylated 1,4-dimethylnaphthalene endoperoxide derivative which is expected to release singlet oxygen on thermolysis at a relatively slow rate at room temperature. Upon the deprotection of the silyl units with fluorine ions, it is expected it to release singlet oxygen at a much higher rate, giving rise to a control over the release of the product. The absorption and the fluorescence measurement with a trap molecule which consumes the generated singlet oxygen reveals promising results for the future work for the control of singlet oxygen generation rates. In the second part of this thesis, we focused on the synthesis of a novel fluorescent sensor of a BODIPY derivative which is capable of sensing Zinc cations. The zinc complex is also expected to have a further usage for the sensing of hyperphosphorylated tau proteins, which are commonly produced in the brains of people with Alzheimer’s disease. With this, it has a potential usage in the field of early detection of Alzheimer’s disease.
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
Cucurbit[7]uril-anchored porphyrin-based multifunctional molecular platform for photodynamic antimicrobial and cancer therapy
(American Chemical Society, 2019) Özkan, Melis; Kumar, Yogesh; Keser, Yağmur; Hadi, Seyed E.; Tuncel, Dönüş
Here we report a photoactive supramolecular assembly that is multifunctional and constructed by covalently linking four receptor molecules (cucurbit[7]uril) to a porphyrin derivative with suitable linkers. While this molecular platform serves very efficiently as a light-triggered broad-spectrum antibacterial agent, owing to its negligible dark cytotoxicity and the presence of host molecules (CB7), it can also be utilized as a vehicle to carry drug molecules for a combined chemo and photodynamic cancer therapy.
Open Access
Energy transfer, photosensitization and sensing with novel bodipy compounds and their supramolecular assemblies
(2017-06) Yeşilgül, Nisa
Fluorescent 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.
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, Bilal
A 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.
Open Access
Metal ion release and signaling in molecular logic gate design
(2016-10) Uyar, Taha Bilal
Mimicking the biological structures is one of the main goals of the natural sciences, because processes are well-organized in nature despite its amazing complexity. On account of this, releasing metal ions at molecular level is a crucial topic owing to similar process in living organisms. In this thesis, we designed novel cage compounds for this purpose. Our novel cage molecule is activated with near-IR light while almost all of the cage compounds in the previous literature function in the UV region. Consequently, it is appropriate for using in biological systems. Release of zinc ions that has critical roles in human body successfully achieved by our novel compound in Part 2 of the thesis work. Molecular logic concept is one of the promising areas of chemistry. Today, electronic devices consists of silicon based circuits that process information by using binary logic. Molecular logic offers alternative for silicon based devices. Using molecules to process data is a promising idea in the fields from electronics to biotechnology. In part 3, we proposed AND gate whose inputs are pH and glutathione while the response is singlet oxygen which can be used to destroy cancer cells. It is possible to process much complicated information by combining more than one logic gate. In first part of the thesis study, we designed modular molecular logic gates by cascading of three logic gates via metal ion signals. In the last part, a fluorescent chemosensor was proposed for dopamine molecule, which is crucial in a number of biological processes at the human body.
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.
Open Access
Photodynamic therapy—current limitations and novel approaches
(Frontiers Research Foundation, 2021-06-10) Ayan, Seylan; Gedik, M. E.; Günaydın, G.
Photodynamic therapy (PDT) mostly relies on the generation of singlet oxygen, via the excitation of a photosensitizer, so that target tumor cells can be destroyed. PDT can be applied in the settings of several malignant diseases. In fact, the earliest preclinical applications date back to 1900’s. Dougherty reported the treatment of skin tumors by PDT in 1978. Several further studies around 1980 demonstrated the effectiveness of PDT. Thus, the technique has attracted the attention of numerous researchers since then. Hematoporphyrin derivative received the FDA approval as a clinical application of PDT in 1995. We have indeed witnessed a considerable progress in the field over the last century. Given the fact that PDT has a favorable adverse event profile and can enhance anti-tumor immune responses as well as demonstrating minimally invasive characteristics, it is disappointing that PDT is not broadly utilized in the clinical setting for the treatment of malignant and/or non-malignant diseases. Several issues still hinder the development of PDT, such as those related with light, tissue oxygenation and inherent properties of the photosensitizers. Various photosensitizers have been designed/synthesized in order to overcome the limitations. In this Review, we provide a general overview of the mechanisms of action in terms of PDT in cancer, including the effects on immune system and vasculature as well as mechanisms related with tumor cell destruction. We will also briefly mention the application of PDT for non-malignant diseases. The current limitations of PDT utilization in cancer will be reviewed, since identifying problems associated with design/synthesis of photosensitizers as well as application of light and tissue oxygenation might pave the way for more effective PDT approaches. Furthermore, novel promising approaches to improve outcome in PDT such as selectivity, bioengineering, subcellular/organelle targeting, etc. will also be discussed in detail, since the potential of pioneering and exceptional approaches that aim to overcome the limitations and reveal the full potential of PDT in terms of clinical translation are undoubtedly exciting. A better understanding of novel concepts in the field (e.g. enhanced, two-stage, fractional PDT) will most likely prove to be very useful for pursuing and improving effective PDT strategies.
Open Access
Towards therapeutic automata and hypoxia activated singlet oxygen generators
(2019-08) Ayan, Seylan
Photodynamic therapy (PDT) is a treatment modality depends on the efficient generation of singlet oxygen (1O2) through excitation of a particular chromophore (sensitizer) followed by an energy transfer to the dissolved oxygen in tumor tissues. Cytotoxic singlet oxygen and other secondary products (reactive oxygen species, ROS) are responsible for the apoptotic and necrotic deaths of the tumor cells. We present a molecular 1:2 demultiplexer (DEMUX) which acts as a "terminator" automaton: once powered up by photoexcitation, the agent releases singlet oxygen to kill cancer cells. Once the cancer cells start apoptosis, the agent interacts with the exposed phosphatidylserines on the external leaflet, and autonomously switches to the signaling mode, turning on a bright emission signal, and turning off singlet oxygen generation. So, the output can switch between singlet oxygen and a confirmatory fluorescence emission for apoptosis, which are mutually exclusive in this design. The automaton that we present here, is based on logic gate considerations and a sound photophysical understanding of the system, and should be a very convincing case of molecular logic with a clear path of progress towards practicality. In another project, we are very much interested in transforming PDT into a more manageable and broadly applicable therapeutic protocol. Our approach to achieve that is to separate photosensitization event from the delivery of singlet oxygen, which is the primary cytotoxic agent of PDT. Thus, a storage compound (endoperoxide) for singlet oxygen has to be designed, which can react with molecular oxygen under typical photosensitization conditions, and then the metastable compound has to be transferred to the tumor site which would release its cargo in response to a chemical or enzymatic cue. This approach assumes that singlet oxygen produced stoichiometrically (as opposed to catalytically through photosensitization) by the chemical transformation of the carrier molecule, would be enough to trigger apoptotic response in cancer cells.