Journal
BIOMACROMOLECULES
Volume 16, Issue 3, Pages 743-747Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bm501659w
Keywords
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Funding
- National Institutes of Health [1R21EB016947-01A1]
- Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231]
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R21EB016947] Funding Source: NIH RePORTER
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Nanoparticles, 10-30 nm in size, have shown great prospects as nanocarriers for drug delivery. We designed amphiphiles based on 3-helix peptide-PEG conjugate forming 15 nm micelles (defined as 3-helix micelles) with good in vivo stability. Here, we investigated the effect of the site of PEG conjugation on the kinetic stability and showed that the conjugation site affects the PEG chain conformation and the overall molecular architecture of the subunit. Compared to the original design where the PEG chain is located in the middle of the 3-helix bundle, micelle kinetic stability was reduced when the PEG chain was attached near the N-terminus (t(1/2) = 35 h) but was enhanced when the PEG chain was attached near the C-terminus (t(1/2) = 80 h). Quantitative structural and kinetic analysis suggest that the kinetic stability was largely dictated by the combined effects of entropic repulsion associated with PEG chain conformation and the geometric packing of the trimeric subunits. The modular design approach coupled with a variety of well-defined protein stucture and functional polymers will significantly expand the utility of these materials as nanocarriers to meet current demands in nanomedine.
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