Nanodrugs based on peptide-modulated self-assembly: Design, delivery and tumor therapy

In this review we consider assembled nanodrugs as a type of nanoscale drugs formed by molecular self-assembly and associated with precise organization of multiple non-covalent interactions. Their typical feature is that the drug itself is considered as one of the building blocks with flexibly interplaying interaction for supramolecular assembly and nanostructure formation with robust stability and high loading efficiency in a controlled and tunable way. The super stability with retained function results from the “hydrophobic effect” of supramolecular self-assembly of peptides and drugs. It is the hydrophobic effect responsible for both colloidal stability and circulation stability in body against dilution and blood-flow shearing. The assembled nanodrugs are distinguished from conventional ones with encapsulation of the drugs in delivery nanocarriers. We will focus on how peptides and peptide-conjugates can be designed for controlling and mediating the formation of the assembled nanodrugs. Emphasis will be put on the rational design of intermolecular interactions between drugs and peptides, in vitro and in vivo drug delivery and antitumor therapeutic effects. Finally, we will discuss the key challenges and promising perspectives of such kind of peptide-mediated assembled nanodrugs for both technical advances and potential clinical translation.