title: Albumin-Folate Conjugates for Drug-targeting in Photodynamic Therapy.
abstract: 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.
authors.affiliation: Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Butzbach
authors.affiliation: 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.
authors.forename: Federico A O
authors.initials: FA
authors.lastname: Rasse-Suriani
authors.affiliation: 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.
authors.forename: M Micaela
authors.initials: MM
authors.lastname: Gonzalez
authors.affiliation: 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.
authors.forename: Franco M
authors.initials: FM
authors.lastname: Cabrerizo
authors.affiliation: Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Epe
mesh_terms: D002243:Carbolines / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D058975:Folate Receptor 1 / Q000235:genetics / Q000378:metabolism*; D005492:Folic Acid / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D012710:Serum Albumin, Bovine
chemical_list: D002243:Carbolines; D058975:Folate Receptor 1; D017319:Photosensitizing Agents; D012710:Serum Albumin, Bovine; D005492:Folic Acid; C010262:norharman