Robust and smart polypeptide-based nanomedicines for targeted tumor therapy

Nanomedicines based on synthetic polypeptides are among the most versatile and advanced platforms for tumor therapy. Notably, several polypeptide-based nanodrugs are currently under human clinical assessments. The previous (pre) clinical studies clearly show that dynamic stability (i.e. stable in circulation while destabilized in tumor) of nanomedicines plays a vital role in their anti-tumor performance. Various strategies have recently been developed to design dynamically stabilized polypeptide-based nanomedicines by e.g. crosslinking the nanovehicles with acid, reactive oxygen species (ROS), glutathione (GSH), or photo-sensitive linkers, inter-crosslinking between vehicles and drugs, introducing pi-pi stacking or lipidlipid interactions in the nanovehicles, chemically conjugating drugs to vehicles, and forming unimolecular micelles. Interestingly, these robust and smart nanodrugs have demonstrated improved tumor targetability, anti-tumor efficacy, as well as safety profiles in different tumor models. In this review, representative strategies to robust and smart polypeptide-based nanomedicines for targeted treatment of varying malignancies are highlighted. The exciting development of dynamic nanomedicines will foresee further increasing clinical translation in the future. (C) 2020 Elsevier B.V. All rights reserved.