Recruiting potent membrane penetrability in tumor cell-targeted protein-only nanoparticles

SERNA, NAROA; SANCHEZ, JULIETA MARÍA; UNZUETA, UGUTZ; SÁNCHEZ-GARCÍA, LAURA; SÁNCHEZ-CHARDI, ALEJANDRO; MANGUES, RAMON; VÁZQUEZ, ESTHER; VILLAVERDE, ANTONIO VILLAVERDE

NANOTECHNOLOGY

IOP PUBLISHING LTD

Año: 2018

0957-4484

The membrane pore-forming activities of the antimicrobial peptide GWH1 have been evaluated in combination with the CXCR4-binding properties of the peptide T22, in self-assembling protein nanoparticles with high clinical potential. The resulting constructs, of 25 nm in size, show a dramatically improved cell penetrability into CXCR4+ cells (more than 10-fold) andenhanced endosomal escape (the lysosomal degradationdropping from 90% to 50 %), when compared with equivalent protein nanoparticles lacking GWH1. These data reveal that GWH1 retains its potent membrane activity in form of nanostructured protein complexes. On the other hand, the specificity of T22 in the CXCR4 receptor binding is subsequently minimized but, unexpectedly, not abolished by the presence of the antimicrobial peptide. The functional combination T22-GWH1 results in 30 % of the nanoparticles entering cells via CXCR4 while also exploiting pore formation. This appears as a sufficiently promising value for further development of GWH1-empowered cell-targeted proteins as nanoscale drug carriers, representing a promising approach to overcome lysosomal degradation of protein nanoparticleswith therapeutic value.