Albumin-folate-conjugates for Drug-targeting in Photodynamic Therapy

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

PHOTOCHEMISTRY AND PHOTOBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016 vol. 92 p. 611 - 619

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 a (FRa), which is over-expressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar b-carboline derivatives as photosensitizers covalently linked to folate-tagged albumin as carrier system. The particles were taken up by KB (human carcinoma) cells within < 90 min and then co-localized with a lysosomal marker. FRa antibodies prevented the uptake and also the corresponding conjugate without folate was not taken up. Accordingly, a folate-albumin-b-carbolinium conjugate proved to be phototoxic, while the corresponding albumin-b-carbolinium conjugates without FA were non-toxic, both with and without irradiation. An excess of free folate as competitor for the FRa-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. Thus, phototoxicity 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.