Nanomedicines meet disordered proteins: A shift from traditional materials and concepts to innovative polymers

Water-soluble nanomedicines have been widely studied for the targeted delivery of drugs for a very long time. As a notable example, biomaterials based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers have been under investigation for nearly half a century. In particular, anticancer drug carriers have been developed under the assumption that the leading mechanism with a therapeutic impact on solid tumors is the enhanced permeability and retention (EPR) effect, which dates back more than three decades. Nevertheless, these (and other) materials and concepts have encountered several barriers in their successful translation into clinical practice, and future nanomedicines need improvements in both passive and active targeting to their site of action. Notions borrowed from recent studies on intrinsically disordered proteins (IDPs) seem promising for enhancing the self-assembly, stimuli-responsiveness, and recognition properties of protein/peptide-based copolymers. Accordingly, IDP-based nanomedicines are ready to give new impetus to more traditional research in this field.