Albumin–Folate Conjugates for Drug‐targeting in Photodynamic Therapy

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 f...

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Autores principales: Butzbach, Kathrin, Rasse Suriani, Federico Ariel Osvaldo, González, M. Micaela, Cabrerizo, Franco Martín, Epe, Bernd
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2016
Materias:
Bioquímica
Photodynamic therapy
Albumin–Folate
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/118446
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-118446
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
Photodynamic therapy
Albumin–Folate
spellingShingle Bioquímica
Photodynamic therapy
Albumin–Folate
Butzbach, Kathrin
Rasse Suriani, Federico Ariel Osvaldo
González, M. Micaela
Cabrerizo, Franco Martín
Epe, Bernd
Albumin–Folate Conjugates for Drug‐targeting in Photodynamic Therapy
topic_facet Bioquímica
Photodynamic therapy
Albumin–Folate
description 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.
format Articulo
Preprint
author Butzbach, Kathrin
Rasse Suriani, Federico Ariel Osvaldo
González, M. Micaela
Cabrerizo, Franco Martín
Epe, Bernd
author_facet Butzbach, Kathrin
Rasse Suriani, Federico Ariel Osvaldo
González, M. Micaela
Cabrerizo, Franco Martín
Epe, Bernd
author_sort Butzbach, Kathrin
title Albumin–Folate Conjugates for Drug‐targeting in Photodynamic Therapy
title_short Albumin–Folate Conjugates for Drug‐targeting in Photodynamic Therapy
title_full Albumin–Folate Conjugates for Drug‐targeting in Photodynamic Therapy
title_fullStr Albumin–Folate Conjugates for Drug‐targeting in Photodynamic Therapy
title_full_unstemmed Albumin–Folate Conjugates for Drug‐targeting in Photodynamic Therapy
title_sort albumin–folate conjugates for drug‐targeting in photodynamic therapy
publishDate 2016
url http://sedici.unlp.edu.ar/handle/10915/118446
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AT rassesurianifedericoarielosvaldo albuminfolateconjugatesfordrugtargetinginphotodynamictherapy
AT gonzalezmmicaela albuminfolateconjugatesfordrugtargetinginphotodynamictherapy
AT cabrerizofrancomartin albuminfolateconjugatesfordrugtargetinginphotodynamictherapy
AT epebernd albuminfolateconjugatesfordrugtargetinginphotodynamictherapy
bdutipo_str Repositorios
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