Recombinant Synthesis of Hybrid Lipid-Peptide Polymer Fusions that Self-Assemble and Encapsulate Hydrophobic Drugs.

Journal Article (Journal Article)

Inspired by biohybrid molecules that are synthesized in Nature through post-translational modification (PTM), we have exploited a eukaryotic PTM to recombinantly synthesize lipid-polypeptide hybrid materials. By co-expressing yeast N-myristoyltransferase with an elastin-like polypeptide (ELP) fused to a short recognition sequence in E. coli, we show robust and high-yield modification of the ELP with myristic acid. The ELP's reversible phase behavior is retained upon myristoylation and can be tuned to span a 30-60 °C. Myristoylated ELPs provide a versatile platform for genetically pre-programming self-assembly into micelles of varied size and shape. Their lipid cores can be loaded with hydrophobic small molecules by passive diffusion. Encapsulated doxorubicin and paclitaxel exhibit cytotoxic effects on 4T1 and PC3-luc cells, respectively, with potencies similar to chemically conjugated counterparts, and longer plasma circulation than free drug upon intravenous injection in mice.

Full Text

Duke Authors

Cited Authors

  • Luginbuhl, KM; Mozhdehi, D; Dzuricky, M; Yousefpour, P; Huang, FC; Mayne, NR; Buehne, KL; Chilkoti, A

Published Date

  • November 2017

Published In

Volume / Issue

  • 56 / 45

Start / End Page

  • 13979 - 13984

PubMed ID

  • 28879687

Pubmed Central ID

  • PMC5909378

Electronic International Standard Serial Number (EISSN)

  • 1521-3773

International Standard Serial Number (ISSN)

  • 1433-7851

Digital Object Identifier (DOI)

  • 10.1002/anie.201704625


  • eng