Peptide-drug conjugates as effective prodrug strategies for targeted delivery

Peptide-drug conjugates (PDCs) represent an important class of therapeutic agents that combine one or more drug molecules with a short peptide through a biodegradable linker. This prodrug strategy uniquely and specifically exploits the biological activities and self-assembling potential of small-molecule peptides to improve the treatment efficacy of medicinal compounds. We review here the recent progress in the design and synthesis of peptide-drug conjugates in the context of targeted drug delivery and cancer chemotherapy. We analyze carefully the key design features in choosing the peptide sequence and linker chemistry for the drug of interest, as well as the strategies to optimize the conjugate design. We highlight the recent progress in the design and synthesis of self-assembling peptide-drug amphiphiles to construct supramolecular nanomedicine and nanofiber hydrogels for both systemic and topical delivery of active pharmaceutical ingredients.

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