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RESEARCH PRODUCT
Albumin-Folate Conjugates for Drug-targeting in Photodynamic Therapy.
Kathrin ButzbachM. Micaela GonzalezFranco M. CabrerizoFederico A. O. Rasse-surianiBernd Epesubject
0301 basic medicineCell Survivalmedicine.medical_treatmentSerum albuminPhotodynamic therapy010402 general chemistry01 natural sciencesBiochemistryPhotodynamic therapyCell Line03 medical and health sciencesFolic AcidmedicineHumansFolate Receptor 1Physical and Theoretical ChemistryCytotoxicityAlbumin conjugatesPhotosensitizing AgentsbiologyChemistryOtras Ciencias QuímicasCiencias QuímicasSerum Albumin BovineGeneral Medicine0104 chemical sciencesB-carbolines030104 developmental biologyTargeted drug deliveryBiochemistryPhotochemotherapyDrug deliveryDrug deliverybiology.proteinFolate receptor 1PhotosensitizationPhototoxicityCIENCIAS NATURALES Y EXACTASConjugateCarbolinesdescription
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. Fil: Butzbach, Kathrin. University of Mainz; Alemania Fil: Rasse Suriani, Federico Ariel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Gonzalez, Maria Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Cabrerizo, Franco Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Epe, Bernd. University of Mainz; Alemania
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-07-01 | Photochemistry and photobiology |