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dc.contributor.author
Di Venosa, Gabriela Mariana
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Vallecorsa, Pablo Daniel
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Giuntini, Francesca
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Mamone, Leandro Ariel
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Batlle, Alcira María del C.
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Vanzuli, Silvia
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Juarranz, Ángeles
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MacRobert, Alexander J.
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Egglestone, Ian M.
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Casas, Adriana Gabriela
dc.date.available
2017-07-26T19:20:54Z
dc.date.issued
2015-02
dc.identifier.citation
Di Venosa, Gabriela Mariana; Vallecorsa, Pablo Daniel; Giuntini, Francesca; Mamone, Leandro Ariel; Batlle, Alcira María del C.; et al.; The use of dipeptide derivatives of 5-aminolaevulinic acid promotes their entry to tumor cells and improves tumor selectivity of photodynamic therapy; American Association for Cancer Research; Molecular Cancer Therapeutics; 14; 2; 2-2015; 440-451
dc.identifier.issn
1535-7163
dc.identifier.uri
http://hdl.handle.net/11336/21366
dc.description.abstract
The use of endogenous protoporphyrin IX generated after administration of 5-aminolaevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). However, the bioavailability of ALA is limited by its hydrophilic properties and limited cell uptake. A promising approach to optimize the efficacy of ALA-PDT is to deliver ALA in the form of prodrugs to mask its hydrophilic nature. The aim of this work was to evaluate the potential of two ALA dipeptide derivatives, N-acetyl terminated leucinyl-ALA methyl ester (Ac-Leu-ALA-Me) and phenylalanyl-ALA methyl ester (Ac-Phe-ALA-Me), for their use in PDT of cancer, by investigating the generation of protoporphyrin IX in an oncogenic cell line (PAM212-Ras), and in a subcutaneous tumor model. In our in vitro studies, both derivatives were more effective than ALA in PDT treatment, at inducing the same protoporphyrin IX levels but at 50- to 100-fold lower concentrations, with the phenylalanyl derivative being the most effective. The efficient release of ALA from Ac-Phe-ALA-Me appears to be consistent with the reported substrate and inhibitor preferences of acylpeptide hydrolase. In vivo studies revealed that topical application of the peptide prodrug Ac-Phe-ALA-Me gave greater selectivity than with ALA itself, and induced tumor photodamage, whereas systemic administration improved ALA-induced porphyrin generation in terms of equivalent doses administered, without induction of toxic effects. Our data support the possibility of using particularly Ac-Phe-ALA-Me both for topical treatment of basal cell carcinomas and for systemic administration. Further chemical fine-tuning of this prodrug template should yield additional compounds for enhanced ALA-PDT with potential for translation to the clinic.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Association for Cancer Research
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Photodynamic Therapy
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Ala
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Tumor Cells
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Otras Medicina Básica
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
The use of dipeptide derivatives of 5-aminolaevulinic acid promotes their entry to tumor cells and improves tumor selectivity of photodynamic therapy
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-08-30T17:12:45Z
dc.journal.volume
14
dc.journal.number
2
dc.journal.pagination
440-451
dc.journal.pais
Estados Unidos
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Filadelfia
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Fil: Di Venosa, Gabriela Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
dc.description.fil
Fil: Vallecorsa, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
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Fil: Giuntini, Francesca. University of Bath; Reino Unido
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Fil: Mamone, Leandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
dc.description.fil
Fil: Batlle, Alcira María del C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
dc.description.fil
Fil: Vanzuli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
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Fil: Juarranz, Ángeles. Universidad Autónoma de Madrid. Facultad de Ciencias; España
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Fil: MacRobert, Alexander J.. University College London; Estados Unidos
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Fil: Egglestone, Ian M.. University of Bath; Reino Unido
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Fil: Casas, Adriana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
dc.journal.title
Molecular Cancer Therapeutics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1158/1535-7163.MCT-13-1084
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://mct.aacrjournals.org/content/14/2/440
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