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 thecytotoxicity of photosensitizers in the presence of light. Increasedselectivity and effectivity of the treatment is expected if a specific uptakeof the photosensitizers into the target cells, often tumor cells, can beachieved. An attractive transporter for that purpose is the folic acid receptor a (FRa), which is over-expressed onthe surface of many tumor cells and mediates an endocytotic uptake. Here, wedescribe the synthesis and photobiological characterization of polar b-carboline derivatives asphotosensitizers covalently linked to folate-tagged albumin as carrier system.The particles were taken up by KB (humannasopharyngeal carcinoma) cells within < 90 min and then co-localized with alysosomal marker. FRa antibodies prevented the uptake and also thecorresponding conjugate without folate was not taken up. Accordingly,a folate-albumin-b-carbolinium conjugate provedto be phototoxic, while the corresponding albumin-b-carbolinium conjugateswithout FA were non-toxic, both with and without irradiation. An excess of freefolate as competitor for the FRa-mediateduptake completely inhibited the photocytotoxicity. Interestingly, the albuminconjugates are devoid of photodynamic activity under cell-free conditions, asshown for DNA as a target. This indicates that the reactive species generatedby photoexcitation of the chromophore are efficiently scavenged by the attachedalbumin so that phototoxiciy requires cellular uptake and lysosomal degradationof the conjugates.