Browsing by Subject "Photodynamic Therapy"
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Item Open Access Chromogenic and fluorogenic sensing of biological thiols in aqueous solutions using BODIPY-based reagents(American Chemical Society, 2013) Isik, M.; Ozdemir, T.; Turan, I. S.; Kolemen, S.; Akkaya, E. U.Judicious design of BODIPY dyes carrying nitroethenyl substituents in conjugation with the BODIPY core yields dyes that respond to biological thiols by both absorbance and emission changes. Incorporation of solubilizing ethyleneglycol units ensures water solubility. The result is bright signaling of biologically relevant thiols in the longer wavelength region of the visible spectrum and in aqueous solutions.Item Open Access Designing BODIPY-based probes for fluorescence imaging of b-amyloid plaques(Royal Society of Chemistry, 2014) Sozmen, F.; Kolemen, S.; Kumada, H. O.; Ono, M.; Saji, H.; Akkaya, E. U.Styryl-congutated BODIPY dyes which are structurally similar to known Ab peptide binding dyes, were designed and synthesized. The binding is accompanied by a large increase in the emission intensity in all cases, suggesting a high potential for use in the fluorescence imaging of Ab plaques.Item 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.Item Open Access Sensing and sensitizer activation by biological thiols and 1,2-dioxetanes based chemiluminescence probes(Bilkent University, 2014) Turan, İlke ŞimşekBiologically 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.Item Open Access Towards mechanochemical generation of singlet oxygen(Bilkent University, 2018-12) Aydonat, SimaySinglet oxygen is a short-lived reactive species which is involved a number of biochemical processes and implicated as the primary photo-generated cytotoxic agent in photodynamic therapy (PDT) of cancer. Precise chemical control of singlet oxygen generation and or storage is therefore of immense interest. In this particular study, the possibility of mechanochemical release of singlet oxygen in cross-linked polymers carrying anthracene 9,10-endoperoxides was explored. 9,10-Diphenylanthracenes are stable at room temperature but undergo thermal cycloreversion when heated to produce singlet oxygen. Thus, a cross-linked polyacrylate was synthesized, incorporating anthracene-endoperoxide modules with chain extensions at the 9,10-positions. Previously in our lab, thermal lability of the anthracene endoperoxides were shown when attached to gold nanorods. In this work, it was demonstrated that on mechanical agitation in a cryogenic ball mill, fluorescence emission due to anthracene units in the polymer is enhanced, with a concomitant generation of singlet oxygen as proved by detection with a selective probe, SOSG. Also, a cross-linked polyacrylate and a PDMS elastomer incorporating anthracene-endoperoxide modules with chain extensions at the 9,10-positions were synthesized as the polymeric matrix for a better manifestation of mechanochemical process.