Hyperbranched Polyglycerol Loaded with (Zinc-)Porphyrins: Photosensitizer Release Under Reductive and Acidic Conditions for Improved Photodynamic Therapy
| Autor: | Katharina Achazi, Michael H. Staegemann, Burkhard Gitter, Susanna Gräfe, Elisa Quaas, Rainer Haag, Arno Wiehe |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Glycerol
Staphylococcus aureus Polymers and Plastics Metalloporphyrins Polymers medicine.medical_treatment Nanoparticle Bioengineering Photodynamic therapy 02 engineering and technology 010402 general chemistry 01 natural sciences Biomaterials Temoporfin chemistry.chemical_compound Cystamine Cell Line Tumor Materials Chemistry medicine Humans Photosensitizer Microscopy Confocal Photosensitizing Agents Cycloaddition Reaction Hydrogen-Ion Concentration Flow Cytometry 021001 nanoscience & nanotechnology Combinatorial chemistry Porphyrin Cycloaddition Anti-Bacterial Agents 0104 chemical sciences Photochemotherapy chemistry Spectrophotometry Ultraviolet Chromatography Thin Layer 0210 nano-technology Acids Oxidation-Reduction Copper Conjugate |
| Zdroj: | Biomacromolecules. 19:222-238 |
| ISSN: | 1526-4602 1525-7797 |
| DOI: | 10.1021/acs.biomac.7b01485 |
| Popis: | 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 copper(I)-catalyzed 1,3-dipolar cycloaddition (CuAAC) or the strain-promoted alkyne-azide cycloaddition (SPAAC) has been developed. The PS 10,15,20-tris(3-hydroxyphenyl)-5-(2,3,4,5,6-pentafluorophenyl)porphyrin 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. |
| Databáze: | OpenAIRE |
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