Peptide-Based Nanostructured Materials with Intrinsic Proapoptotic Activities in CXCR4+ Solid Tumors

5 years ago

Peptide-Based Nanostructured Materials with Intrinsic Proapoptotic Activities in CXCR4+ Solid Tumors

Neus Ferrer-Miralles, Alejandro Sánchez-Chardi, Laura Sánchez-García, Ramón Mangues, María Virtudes Céspedes, Ugutz Unzueta, Naroa Serna, Francisco Cortés, Rita Sala, Antonio Villaverde, Esther Vázquez

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. A new category of biomaterials is developed in which therapeutic peptides self-assemble as intrinsically functional protein-only nanoparticles, acting as targeted drugs. Several unrelated tumor-targeted proapoptotic proteins are administered in cancer models in form of chemically homogenous assemblies, with a size over the threshold of renal clearance. These materials promote targeted apoptosis and necrosis in colorectal cancer tissues upon systemic administration.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adfm.201700919