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.