Peptide-Based Nanostructured Materials with Intrinsic Proapoptotic Activities in CXCR4+ Solid Tumors
￼Naroa Serna, ￼María Virtudes Céspedes, ￼Laura Sánchez-García, ￼Ugutz Unzueta, ￼Rita Sala, ￼Alejandro Sánchez-Chardi, ￼Francisco Cortés, ￼Neus Ferrer-Miralles, ￼Ramón Mangues, ￼Esther Vázquez, ￼Antonio Villaverde
Protein materials are gaining interest in nanomedicine because of the unique combination of regulatable function and structure. A main application of protein nanoparticles is as vehicles for cell-targeted drug delivery in the form of nanoconjugates, in which a conventional or innovative drug is associated to a carrier protein. Here, a new nanomedical approach based on self-assembling protein nanoparticles is developed in which a chemically homogeneous protein material acts, simultaneously, as vehicle and drug. For that, three proapoptotic peptidic factors are engineered to self-assemble as protein-only, fully stable nanoparticles that escape renal clearance, for the multivalent display of a CXCR4 ligand and the intracellular delivery into CXCR4+ colorectal cancer models. These materials, produced and purified in a single step from bacterial cells, show an excellent biodistribution upon systemic administration and local antitumoral effects. The design and generation of intrinsically therapeutic protein-based materials offer unexpected opportunities in targeted drug delivery based on fully biocompatible, tailor-made constructs.