Peptide-drug conjugates as effective prodrug strategies for targeted delivery

Yin Wang; Andrew G Cheetham; Garren Angacian; Hao Su; Lisi Xie; Honggang Cui

doi:10.1016/j.addr.2016.06.015

Peptide-drug conjugates as effective prodrug strategies for targeted delivery

Adv Drug Deliv Rev. 2017 Feb:110-111:112-126. doi: 10.1016/j.addr.2016.06.015. Epub 2016 Jun 29.

Authors

Yin Wang¹, Andrew G Cheetham¹, Garren Angacian², Hao Su¹, Lisi Xie¹, Honggang Cui³

Affiliations

¹ Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA; Institute for NanoBioTechnology, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA.
² Department of Biomedical Engineering, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA.
³ Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA; Institute for NanoBioTechnology, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA; Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA.

Abstract

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.

Keywords: Cancer; Conjugated chemistry; Drug amphiphiles; Drug delivery; Peptide–drug conjugates.

Publication types

Review

MeSH terms

Animals
Drug Delivery Systems / methods*
Drug Design
Humans
Hydrogels / administration & dosage
Hydrogels / chemistry
Nanofibers / administration & dosage
Nanofibers / chemistry
Neoplasms / drug therapy
Peptides / administration & dosage
Peptides / chemistry*
Prodrugs / administration & dosage*
Prodrugs / therapeutic use

Substances

Hydrogels
Peptides
Prodrugs

Abstract

Publication types

MeSH terms

Substances

Grants and funding