Peptide-Drug Conjugates (PDCs)

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugate (ADCs) and hold broad prospects in fields such as tumor treatment. PDCs combine peptides selectivity with chemotherapeutic drugs lethality, with the core benefits of enhanced cellular permeability and improved drug selectivity. PDCs consist of three important components: peptides, linkers and cytotoxic payloads. Among them, peptides mainly include homing peptides and cell-penetrating peptides, which can affect the efficiency of drug endocytosis. The ideal peptide should have high affinity, stability, and so on. Cytotoxins is the key to killing tumor cells and has both therapeutic and imaging functions. Cytotoxins for coupling have four requirements as followed: a clear mechanism of action, a small molecular weight, high cytotoxicity and retained anti-tumor activity after chemical coupling to the peptide. The linker needs to connect the peptide and the cytotoxic payload and can be divided into cleavable and non-cleavable types. The choice of linker is crucial and requires consideration of the microenvironment in which the PDC is located to avoid interfering with the binding affinity of the peptide to its receptor and the drug efficacy. The linker must have a certain level of stability to prevent premature and nonspecific drug release^[1].