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

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

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.

from ! Medicine by Alexandros G. Sfakianakis via Αλέξανδρος Σφακιανάκης on Inoreader http://ift.tt/2sLBdCo
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