Título:
Targeted-lymphoma drug delivery system based on the Sgc8-c aptamer
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Autor:
Sicco, Estefanía
Cerecetto, Hugo
Calzada, Victoria
Moreno, María
Cerecetto, Hugo
Calzada, Victoria
Moreno, María
Tutor:
Tipo de documento:
Artículo
Editor:
Palabras clave:
Lymphoma
Aptamer
Drug delivery
Aptamer-drug conjugates
Biotherapeutics
PTK7
Aptamer
Drug delivery
Aptamer-drug conjugates
Biotherapeutics
PTK7
Descriptores:
Año de publicación:
2023
Contenido:
Resumen:
Aptamers are emerging as a promising new class of functional nucleic acids because they can specifically bind to any target with high affinity and be easily modified chemically with different pharmacophoric subunits for therapy. The truncated aptamer, Sgc8-c, binds to tyrosine-protein kinaselike 7 receptor, a promising cancer therapeutic target, allowing the recognition of haemato-oncological malignancies, among others. We have previously developed aptamer-drug conjugates by chemical synthesis, hybridizing Sgc8-c and dasatinib, a drug proposed for lymphoma chemotherapy. One of the best-characterised Sgc8-c-dasatinib hybrids, namely Sgc8-c-carb-da, was capable of releasing dasatinib at an endosomal-pH. Herein, we probed the therapeutic potential of this aptamer-drug conjugate. Sgc8-c-carb-da specifically inhibited murine A20 B lymphocyte growth and produced cell death, mainly by late apoptosis and necrosis. In addition, Sgc8-c-carb-da generated an arrest in cell proliferation, with a cell cycle arrest in the Sub-G1-peak. The mitochondrial potential was altered accordingly to these pathways. Moreover, using an in vitro cell-targeting assay that mimics in vivo conditions, we showed that Sgc8-c-carb-da displayed higher (2.5-fold) cytotoxic effects than dasatinib. These findings provide proof-of-concept of the therapeutic value of Sgc8-c-carb-da for lymphoma, creating new opportunities for the chemical synthesis of targeted biotherapeutics.
Descripción:
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Editorial:
MDPI
EN:
Cancers, 2023, 15(3): 922.
Financiadores:
ANII: POS_NAC_2017_1_140364
Citación:
Sicco, E, Cerecetto, H, Calzada, V [y otros autores]. "Targeted-lymphoma drug delivery system based on the Sgc8-c aptamer". Cancers. [en línea] 2023, 15(3): 922. 13 h. DOI: 10.3390/cancers15030922.
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ISSN:
2072-6694
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Licencia:
Licencia Creative Commons Atribución (CC - By 4.0)
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| Ficheros | Descripción | Tamaño | Formato | ||
|---|---|---|---|---|---|
| 10.3390.cancers15030922.pdf | — | 2.18 MB | Adobe PDF |