Oxidized low-density lipoprotein as a delivery system for photosensitizers: Implications for photodynamic therapy of atherosclerosis

Photodynamic therapy is a promising new strategy in the treatment of cardio vascular diseases. Photodynamic therapy for vascular diseases may be improv ed by the specific delivery of photosensitizers to the atherosclerotic lesi on. In this study, we studied whether oxidatively modified low-density lipo protein (OxLDL) could be used as a specific carrier for photosensitizers, t hereby using the scavenger receptor expressed on macrophages as a target. T he photosensitizer aluminum phthalocyanine chloride (AlPc) was incorporated into OxLDL, and its photodynamic effects were studied. Macrophages (RAW 26 4.7) were incubated with various concentrations of OxLDL-AlPc for different periods. After illumination of the cells with red right, cytotoxicity was observed that was dependent on the time of illumination and incubation. Mac rophages incubated with OxLDL-AlPc that were not illuminated revealed no cy totoxicity; The uptake of the OxLDL-AlPc complexes was mediated by scavenge r receptors expressed on macrophages. In the presence of the polyanion poly inosinic acid, a specific ligand for scavenger receptors,no cytotoxicity co uld be observed. Serum incubations of the OxLDL-AlPc complexes revealed tha t these complexes stay intact after incubation. No redistribution of AlPc t o other plasma (lipo-) proteins could: be detected, and 80-90% of the AlPc remained associated with the OxLDL particle. These results indicate that Ox LDL may function as a specific delivery system for photosensitizers to the scavenger receptors expressed on the macrophages in the atherosclerotic les ion, increasing the beneficial effects of photodynamic therapy for cardiova scular diseases.