Capturing “Extraordinary” Soft-Assembled Charge-Like Polypeptides as a Strategy for Nanocarrier Design
Aroa Duro-Castano, Vicent J. Nebot,* Amaya Niño-Pariente, Ana Armiñán, Juan J. Arroyo-Crespo, Alison Paul, Natalia Feiner-Gracia, Lorenzo Albertazzi, and María J. Vicent*


The rational design of nanomedicines is a challenging task given the com-plex architectures required for the construction of nanosized carriers with embedded therapeutic properties and the complex interface of these mate-rials with the biological environment. Herein, an unexpected charge-like attraction mechanism of self-assembly for star-shaped polyglutamates in nonsalty aqueous solutions is identified, which matches the ubiquitous“ordinary–extraordinary” phenomenon previously described by physicists. For the first time, a bottom-up methodology for the stabilization of these nano-sized soft-assembled star-shaped polyglutamates is also described, enablingthe translation of theoretical research into nanomaterials with applicability within the drug-delivery field. Covalent capture of these labile assemblies provides access to unprecedented architectures to be used as nanocarriers. The enhanced in vitro and in vivo properties of these novel nanoconstructs as drug-delivery systems highlight the potential of this approach for tumor- localized as well as lymphotropic delivery.