Multifunctional building elements for the construction of peptide drug conjugates

Abstract

• This review presents special attention to the role and importance of structural characteristics of self-assembling peptides, transformable peptide-drug conjugates, targeting peptides and cell-penetrating peptides. • This review provides useful guidelines for the design of linker segment for intelligent and controllable cargo release. • Summarize the peptide-drug conjugates in development and clinical trials and arouse widespread attention to peptide-drug conjugate design strategies and their contribution in fighting various diseases. Engineering of smart building molecules is key basis in designing intelligent drug delivery systems. As an emerging sophisticated delivery system strategy, the powerful functions of peptide drug conjugates (PDCs) are attributed to a smart linker and multifunctional peptide domain. Peptides exhibit a wide range of functions and properties, including easy chemical synthesis and versatile modification, tunable biocompatibility, diversified self-assembled nanostructures, specific recognition/binding, and deep penetration of the cell membrane/extracellular matrix. In addition, various types of linkers enable PDCs to release drugs responsively according to the disease microenvironment or treatment needs. Owing to these inherent advantages, PDCs have been widely explored for drug delivery. Herein, the latest developments in functional peptides and linkers commonly used to construct smart PDCs are reviewed. The purpose is to bring widespread attention to PDC design strategies and their contribution to fighting various diseases, as well as to provide guidance for research on intelligent PDC drug delivery systems.