Albumin-Folate Conjugates for Drug-targeting in Photodynamic Therapy.

Autor: Butzbach K; Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany., Rasse-Suriani FA; Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Chascomús, Argentina., Gonzalez MM; Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Chascomús, Argentina., Cabrerizo FM; Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Chascomús, Argentina., Epe B; Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.
Jazyk: angličtina
Zdroj: Photochemistry and photobiology [Photochem Photobiol] 2016 Jul; Vol. 92 (4), pp. 611-9. Date of Electronic Publication: 2016 Jul 07.
DOI: 10.1111/php.12602
Abstrakt: 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 overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar β-carboline derivatives as photosensitizers covalently linked to folate-tagged albumin as the carrier system. The particles were taken up by KB (human carcinoma) cells within <90 min and then co-localized with a lysosomal marker. FRα antibodies prevented the uptake and also the corresponding conjugate without folate was not taken up. Accordingly, a folate-albumin-β-carbolinium conjugate proved to be phototoxic, while the corresponding albumin-β-carbolinium conjugates without FA were nontoxic, 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. 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.
(© 2016 The American Society of Photobiology.)
Databáze: MEDLINE
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