In Vivo Translation of Peptide-Targeted Drug Delivery Systems Discovered by Phage Display

Therapeutic compounds with narrow therapeutic windows and significant systemic side effects benefit from targeted drug delivery strategies. Peptide-protein interactions are often exploited for targeting, with phage display a primary method to identify high-affinity peptide ligands that bind cell surface and matrix bound receptors preferentially expressed in target tissues. After isolating and sequencing high-binding phages, peptides are easily synthesized and chemically modified for incorporation into drug delivery systems, including peptide-drug conjugates, polymers, and nanoparticles. This review describes the phage display methodology to identify targeting peptide sequences, strategies to functionalize drug carriers with phage-derived peptides, specific examples of drug carriers with in vivo translation, and limitations and future applications of phage display to drug delivery.