Engineering a Nanostructured Nucleolin-Binding Peptide for Intracellular Drug Delivery in Triple-Negative Breast Cancer Stem Cells

M. Pesarrodona, L. Sánchez-García, J. Seras-Franzoso, A. Sánchez-Chardi, R. Baltá-Foix, P. Cámara-Sánchez, P. Gener, J.J. Jara, D. Pulido, N. Serna, S. Schwartz, M. Royo, A. Villaverde, I. Abasolo, Esther Vazquez Gomez

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Resum

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)n, 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.
Idioma originalEnglish
Pàgines (de-a)5381–5388
Nombre de pàgines8
RevistaACS Applied Materials and Interfaces
Volum12
Número5
DOIs
Estat de la publicacióPublicada - 2020

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