Intracellular PDT activity of a pegylated form of meso-tetra-(hydroxy-phenyl)-chlorin (mTHPC)

摘要

Abstract: In the presented study, the intracellular PDT efficiency of a new poly-ethylene glycol (PEG) derivative of meso-tetra- chlorin (mTHPC) was tested in a cell culture model and the PDT dose-efficiency dependence determined using mTHPC as a reference. Squamous cell carcinoma cells incubated with mTHPC or mTHPC-PEG in 96-well microplates were irradiated with laser light. Cell viability was determined at several timepoints after irradiation by an MTS cell proliferation assay. Equal products of irradiant energy and applied doses of mTHPC-PEG, or mTHPC respectively, yielded identical PDT effects on the cells. PDT efficiency depended in a threshold-like manner on the applied light and sensitizer doses for either compound. For mTHPC-PEG, below 250 (ng/ml)*(J/cm$+2$/) no effect could be detected; with 1250 (ng/ml)*(J/cm$+2$) and more, all cells were killed. mTHPC was 20 fold more effective than mTHPC-PEG. Since mTHPC-PEG shows higher tumor accumulation rates in several animal models than mTHPC, appropriate parameters and clinical applications should be found where the pegylation further enhances the potential of mTHPC PDT< although mTHPC-PEG is less effective than the free compound in vitro. In conclusion, the new mTHPC-PEG conjugate as a macromolecular and water-soluble variation of mTHPC shows intracellular PDT efficiency and therefore holds the potential for an improved mTHPC PDT. !9