@article{KošćakPeharBožinovićetal.2022, author = {Košćak, Marta and Pehar, Isabela and Božinović, Ksenija and Kole, Goutam Kumar and Sobočanec, Sandra and Podgorski, Iva I. and Pinterić, Marija and M{\"u}ller-Buschbaum, Klaus and Majhen, Dragomira and Piantanida, Ivo and Marder, Todd B.}, title = {Para-N-methylpyridinium pyrenes: impact of positive charge on ds-DNA/RNA and protein recognition, photo-induced bioactivity, and intracellular localisation}, series = {Pharmaceutics}, volume = {14}, journal = {Pharmaceutics}, number = {11}, issn = {1999-4923}, doi = {10.3390/pharmaceutics14112499}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297247}, year = {2022}, abstract = {The 2- and 2,7- substituted para-N-methylpyridinium pyrene cations show high-affinity intercalation into ds-DNAs, whereas their non-methylated analogues interacted with ds-DNA/RNA only in the protonated form (at pH 5), but not at physiological conditions (pH 7). The fluorescence from non-methylated analogues was strongly dependent on the protonation of the pyridines; consequently, they act as fluorescence ratiometric probes for simultaneous detection of both ds-DNA and BSA at pH 5, relying on the ratio between intensities at 420 nm (BSA specific) and 520 nm (DNA specific), whereby exclusively ds-DNA sensing could be switched-off by adjustment to pH 7. Only methylated, permanently charged pyrenes show photoinduced cleavage of circular DNA, attributed to pyrene-mediated irradiation-induced production of singlet oxygen. Consequently, the moderate toxicity of these cations against human cell lines is strongly increased upon irradiation. Detailed studies revealed increased total ROS production in cells treated by the compounds studied, accompanied by cell swelling and augmentation of cellular complexity. The most photo-active 2-para-N-methylpyridinium pyrene showed significant localization at mitochondria, its photo-bioactivity likely due to mitochondrial DNA damage. Other derivatives were mostly non-selectively distributed between various cytoplasmic organelles, thus being less photoactive.}, language = {en} } @phdthesis{Grebinyk2021, author = {Grebinyk, Anna}, title = {Synergistic Chemo- and Photodynamic Treatment of Cancer Cells with C\(_{60}\) Fullerene Nanocomplexes}, doi = {10.25972/OPUS-22207}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222075}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Recent progress in nanotechnology has attracted interest to a biomedical application of the carbon nanoparticle C60 fullerene (C60) due to its unique structure and versatile biological activity. In the current study the dual functionality of C60 as a photosensitizer and a drug nanocarrier was exploited to improve the efficiency of chemotherapeutic drugs towards human leukemic cells. Pristine C60 demonstrated time-dependent accumulation with predominant mitochondrial localization in leukemic cells. C60's effects on leukemic cells irradiated with high power single chip LEDs of different wavelengths were assessed to find out the most effective photoexcitation conditions. A C60-based noncovalent nanosized system as a carrier for an optimized drug delivery to the cells was evaluated in accordance to its physicochemical properties and toxic effects. Finally, nanomolar amounts of C60-drug nanocomplexes in 1:1 and 2:1 molar ratios were explored to improve the efficiency of cell treatment, complementing it with photodynamic approach. A proposed treatment strategy was developed for C60 nanocomplexes with the common chemotherapeutic drug Doxorubicin, whose intracellular accumulation and localization, cytotoxicity and mechanism of action were investigated. The developed strategy was revealed to be transferable to an alternative potent anticancer drug - the herbal alkaloid Berberine. Hereafter, a strong synergy of treatments arising from the combination of C60-mediated drug delivery and C60 photoexcitation was revealed. Presented data indicate that a combination of chemo- and photodynamic treatments with C60-drug nanoformulations could provide a promising synergetic approach for cancer treatment.}, subject = {cancer}, language = {en} } @article{WaeldchenLehmannKleinetal.2015, author = {W{\"a}ldchen, Sina and Lehmann, Julian and Klein, Teresa and van de Linde, Sebastian and Sauer, Markus}, title = {Light-induced cell damage in live-cell super-resolution microscopy}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, number = {15348}, doi = {10.1038/srep15348}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145207}, year = {2015}, abstract = {Super-resolution microscopy can unravel previously hidden details of cellular structures but requires high irradiation intensities to use the limited photon budget efficiently. Such high photon densities are likely to induce cellular damage in live-cell experiments. We applied single-molecule localization microscopy conditions and tested the influence of irradiation intensity, illumination-mode, wavelength, light-dose, temperature and fluorescence labeling on the survival probability of different cell lines 20-24 hours after irradiation. In addition, we measured the microtubule growth speed after irradiation. The photo-sensitivity is dramatically increased at lower irradiation wavelength. We observed fixation, plasma membrane permeabilization and cytoskeleton destruction upon irradiation with shorter wavelengths. While cells stand light intensities of similar to 1 kW cm\(^{-2}\) at 640 nm for several minutes, the maximum dose at 405 nm is only similar to 50 J cm\(^{-2}\), emphasizing red fluorophores for live-cell localization microscopy. We also present strategies to minimize phototoxic factors and maximize the cells ability to cope with higher irradiation intensities.}, language = {en} } @article{MansourArevaloAlKahtanietal.2014, author = {Mansour, Ahmad M. and Arevalo, J. Fernando and Al Kahtani, Eman and Zegarra, Hernando and Abboud, Emad and Anand, Rajiv and Ahmadieh, Hamid and Sisk, Robert A. and Mirza, Salman and Tuncer, Samuray and Navea Tejerina, Amparo and Mataix, Jorge and Ascaso, Francisco J. and Pulido, Jose S. and Guthoff, Rainer and Goebel, Winfried and Roh, Young Jung and Banker, Alay S. and Gentile, Ronald C. and Alonso Martinez, Isabel and Morris, Rodney and Panday, Neeraj and Min, Park Jung and Merce, Emilie and Lai, Timothy Y. Y. and Massoud, Vicky and Ghazi, Nicola G.}, title = {Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma}, series = {Journal of Ophtamology}, journal = {Journal of Ophtamology}, number = {210458}, doi = {10.1155/2014/210458}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117923}, pages = {8}, year = {2014}, abstract = {We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.}, language = {en} }