Título:
|
Engineering a nanostructured nucleolin-binding peptide for intracellular drug delivery in triple-negative breast cancer stem cells
|
Autor/a:
|
Pesarrodona Roches, Mireia; Sánchez-García, Laura; Seras-Franzoso, Joaquin; Sánchez Chardi, Alejandro; Baltà Foix, Ricardo; Cámara-Sánchez, Patricia; Gener, Petra; Jara, José Juan; Pulido, Daniel; Serna, Naroa; Schwartz, Simó; Royo, Miriam; Villaverde Corrales, Antonio; Abasolo, Ibane; Vázquez Gómez, Esther; Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia
|
Abstract:
|
Altres ajuts: La Fundació Marató TV3 (TV32013-133930-1-2), AECC post-doctoral fellowship (AIO14142112SERA) i ICREA Academia award |
Abstract:
|
Five peptide ligands of four different cell surface receptors (nucleolin, CXCR1, CMKLR1, and CD44v6) have been evaluated as targeting moieties for triple-negative human breast cancers. Among them, the peptide F3, derived from phage display, promotes the fast and efficient internalization of a genetically fused green fluorescent protein (GFP) inside MDA-MB-231 cancer stem cells in a specific receptor-dependent fashion. The further engineering of this protein into the modular construct F3-RK-GFP-H6 and the subsequent construct F3-RK-PE24-H6 resulted in self-assembling polypeptides that organize as discrete and regular nanoparticles. These materials, 15-20 nm in size, show enhanced nucleolin-dependent cell penetrability. We show that the F3-RK-PE24-H6, based on the Pseudomonas aeruginosa exotoxin A (PE24) as a core functional domain, is highly cytotoxic over target cells. The combination of F3, the cationic peptide (RK), and the toxin domain PE24 in such unusual presentation appears as a promising approach to cell-targeted drug carriers in breast cancers and addresses selective drug delivery in otherwise difficult-to-treat triple-negative breast cancers. |
Materia(s):
|
-Self-assembling polypeptides -Targeting -Nucleolin -Triple-negative breast cancer -Cancer stem cells |
Derechos:
|
open access
Tots els drets reservats.
https://rightsstatements.org/vocab/InC/1.0/ |
Tipo de documento:
|
Article |
Editor:
|
|
Compartir:
|
|
Uri:
|
https://ddd.uab.cat/record/233717
|