Abstract & Authors:展开
By the appropriate selection of functional peptides and proper accommodation sites, we have generated a set of multifunctional proteins that combine selectivity for CXCR4+ cell binding and relevant endosomal escape capabilities linked to the viral peptide HA2. In particular, the construct T22-GFP-HA2-H6 forms nanoparticles that upon administration in mouse models of human, CXCR4+ colorectal cancer, accumulates in primary tumor at levels significantly higher than the parental T22-GFP-H6 HA2-lacking version. The in vivo application of a CXCR4 antagonist has confirmed the prevalence of the CXCR4+ tumor tissue selectivity over unspecific cell penetration, upon systemic administration of the material. Such specificity is combined with improved endosomal escape, what overall results in a precise and highly efficient tumor biodistribution. These data strongly support the functional recruitment as a convenient approach to generate protein materials for clinical applications. More precisely, they also support the unexpected concept that enhancing the unspecific membrane activity of a protein material does not necessarily compromise, but it can even improve, the selective cell targeting offered by an accompanying functional module.
Rita Sala,Laura Sánchez-García
Ramón Mangues,Antonio Villaverde
Rita Sala,Laura Sánchez-García,Naroa Serna,María Virtudes Céspedes,Isolda Casanova,Mònica Roldán,Alejandro Sánchez-Chardi,Ugutz Unzueta,Esther Vázquez,Ramón Mangues,Antonio Villaverde