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
Language
- eng