Albumin-folate-conjugates for drug-targeting in photodynamic therapy

BUTZBACH KATHRIN; RASSE SURIANI FEDERICO A. O.; GONZALEZ M. MICAELA; CABRERIZO FRANCO M.; EPE BERND

PHOTOCHEMISTRY AND PHOTOBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016

0031-8655

Photodynamic therapy (PDT) is based on the cytotoxicity of photosensitizers in the presence of light. Increased selectivity and effectivity of the treatment is expected if a specific uptake of the photosensitizers into the target cells, often tumor cells, can be achieved. An attractive transporter for that purpose is the folic acid receptor α (FRα), which is over-expressed on the surface of many tumor cells and mediates an efficient endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar β-carboline derivatives as photosensitizers covalently linked to albumin, which in turn is conjugated with folate residues as targeting moieties. The particles, which consisted of approx. 1 β-carboline and 7-9 folate residues per albumin molecule, were taken up by KB (human nasopharyngeal carcinoma) cells within < 90 min and then co-localized with a lysosomal marker. Under the same conditions, the corresponding conjugate without folate was not taken up by the cells. Accordingly, a folate-albumin-β-carbolinium conjugate proved to be cytotoxic in the presence of light, while the corresponding albumin-β-carbolinium conjugates without FA were non-toxic, both with and without irradiation. An excess of free folate as competitor for the FRα-mediated uptake completely inhibited the photocytotoxicity. Interestingly, the albumin conjugates are devoid of photodynamic activity under cell-free conditions, as shown for DNA as a target. This indicates that the reactive species generated by photoexcitation of the chromophore are efficiently quenched or scavenged by the attached albumin so that phototoxiciy requires cellular uptake and lysosomal degradation of the conjugates. In conclusion, albumin-folate-conjugates appear to be promising vehicles for a tumor cell targeted PDT.