2 research outputs found
Hyperbranched Polyglycerol Loaded with (Zinc-)Porphyrins: Photosensitizer Release Under Reductive and Acidic Conditions for Improved Photodynamic Therapy
An
adaptable approach toward cleavable nanoparticle carrier systems
for photodynamic therapy (PDT) is presented, comprising a biocompatible
carrier loaded with multiple photosensitizer (PS) molecules related
to the clinically employed PS Temoporfin, two linkers cleavable under
different triggers and glyco-targeting with mannose. A synthetic pathway
to stimuli responsive hyperbranched polyglycerol (hPG) porphyrin conjugates
via the copperÂ(I)-catalyzed 1,3-dipolar cycloaddition (CuAAC) or the
strain-promoted alkyne–azide cycloaddition (SPAAC) has been
developed. The PS 10,15,20-trisÂ(3-hydroxyphenyl)-5-(2,3,4,5,6-pentafluorophenyl)Âporphyrin
was functionalized with disulfide containing cystamine and acid-labile
benzacetal linkers. Conjugates with reductively and pH labile linkers
were thus obtained. Cleavage of the active PS agents from the polymer
carrier is shown in several different release studies. The uptake
of the conjugates into the cells is demonstrated via confocal laser
scanning microscopy (CLSM) and flow cytometry. Finally, the antitumor
and antibacterial phototoxicity of selected conjugates has been assessed
in four different tumor cell lines and in cultures of the bacterium Staphylococcus aureus. The conjugates exhibited phototoxicity
in several tumor cell lines in which conjugates with reductively cleavable
linkers were more efficient compared to conjugates with acid-cleavable
linkers. For S. aureus, strong phototoxicity
was observed for a combination of the reductively cleavable and the
pH labile linker and likewise for the cleavable conjugate with mannose
targeting groups. The results thus suggest that the conjugates have
potential for antitumor as well as antibacterial PDT
Drug quantification in turbid media by fluorescence imaging combined with light-absorption correction using white Monte Carlo simulations
Accurate quantification of photosensitizers is in many cases a critical issue in photodynamic therapy. As a noninvasive and sensitive tool, fluorescence imaging has attracted particular interest for quantification in pre-clinical research. However, due to the absorption of excitation and emission light by turbid media, such as biological tissue, the detected fluorescence signal does not have a simple and unique dependence on the fluorophore concentration for different tissues, but depends in a complex way on other parameters as well. For this reason, little has been done on drug quantification in vivo by the fluorescence imaging technique. In this paper we present a novel approach to compensate for the light absorption in homogeneous turbid media both for the excitation and emission light, utilizing time-resolved fluorescence white Monte Carlo simulations combined with the Beer-Lambert law. This method shows that the corrected fluorescence intensity is almost proportional to the absolute fluorophore concentration. The results on controllable tissue phantoms and murine tissues are presented and show good correlations between the evaluated fluorescence intensities after the light-absorption correction and absolute fluorophore concentrations. These results suggest that the technique potentially provides the means to quantify the fluorophore concentration from fluorescence images