Albumin-Folate-Conjugates as a Potential Targeting Vehicle in Photodynamic Therapy

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

Córdoba

Congreso; 16th international Congress on Photobiology; 2014

In photodynamic therapy (PDT) cells are killed by irradiation in the presence of a photosensitizer, which produces cytotoxic reactive oxygen species (ROS). Specific uptake and accumulation of a photosensitizer in malignant cells, while surrounding tissue stays unaffected, would make this therapeutical concept more powerful and minimal invasive. A possible way to obtain that is to address tumor specific surface molecules. Many solid tumors overexpress folic acid receptor a (FRa), to ensure the supply of folic acid (FA). FRa is an endocytotic receptor with a high FA affinity and a fast turnover rate which makes it an attractive vehicle for cancer cell specific drug delivery. We wanted to find out whether albumin-folateconjugates are useful to transport photosensitizers into FRa overexpressing cancer cells. As a diagnostic tool we used the highly fluorescent b-carboline derivate N2-carboxypropyl-norharmane, which we coupled covalently to BSA. Afterwards we coupled FA to this albumin-b-carboline-conjugate (AbC) to produce an albumin-b-carboline-FA-conjugate (AbCF). These two different conjugates were characterized with respect to size, conjugation pattern and photophysical properties. The fluorescence quantum yield of the fluorophor was not diminished significantly by albumin therefore this conjugate is a suitable molecule to visualize AbCF under the microscope. For delivery studies we used KB cells (human nasopharyngal carcinoma), which are FRa overexpressing. We could show that AbCF accumulates in the lysosomes of the cells with increasing incubation time while AbC is not entering the cell. This proves that the uptake of AbCF is mainly FA mediated. By using a b-carboline derivate with a higher triplet quantum yield and a comparable coupling behavior (e.g. N2-carboxypropyl-harmine) it should be possible to selective kill FRa positive cells by irradiation.